Basics Virology Flashcards
What is the definition of a virus?
A virus is an obligate intracellular parasite. Accordingly, it can only survive within a host cell and depends on it for replication and metabolic processes.
Virion:
The infective form of a virus when it is present outside of cells is called a virion. It is the complete, fully formed viral particle that is capable of infecting a host cell. The virion consists of three main components:
a. DNA or RNA:
The genetic material of a virus can be either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid). DNA and RNA are molecules that carry genetic information. The viral genetic material contains the instructions necessary for the virus to replicate and produce new viral particles.
b. Protein Capsid:
The genetic material of the virus is surrounded by a protective protein coat called the capsid. The capsid provides structural support and helps protect the genetic material from damage. It also determines the shape of the virus. The capsid is made up of repeating protein subunits called capsomeres.
c. Envelope (optional):
Some viruses have an additional outer layer called an envelope. The envelope is derived from the host cell’s membrane and contains a combination of viral and host cell components. It surrounds the capsid and helps the virus enter and exit host cells. The presence of an envelope can affect the virus’s ability to survive outside the host and its susceptibility to certain environmental conditions or host immune responses.
When a virus infects a host cell, it attaches to specific receptors on the cell surface and enters the cell. Inside the host cell, the virus uses the cellular machinery to replicate its genetic material, produce viral proteins, and assemble new viral particles. Once the new virus particles are formed, they can leave the infected cell to infect other cells and continue the infection cycle.
It’s important to note that viruses are different from other microorganisms like bacteria or fungi. They lack the ability to carry out essential life processes such as metabolism, growth, or reproduction on their own. Instead, they rely on hijacking the cellular machinery of a host organism to replicate and spread.
Virion is ________
The infective form of a virus when present outside of cells, which consists of DNA or RNA, a protein capsid, and sometimes an envelope.
What is the difference between Virus and Virion:
Classification of Viral Genome:
Viruses can be either DNA or RNA viruses:
A viral genome refers to the complete genetic material of a virus. It contains all the necessary information for the virus to replicate and produce new viral particles. Viral genomes can be composed of either DNA or RNA, and they can have different structures and arrangements.
🔸DNA Viruses:
DNA viruses have genomes made up of DNA molecules. There are two types of DNA genomes: Double-stranded DNA (dsDNA) and Single-stranded DNA (ssDNA).
- Double-stranded DNA genomes (dsDNA): Most DNA viruses have this type of genome. It means that both strands of the DNA molecule are present and complementary to each other.
- Single-stranded DNA genomes (ssDNA): Some viruses, like those belonging to the Parvoviridae family, have single-stranded DNA genomes. This means that only one of the DNA strands is present.
DNA genomes can also have different shapes or arrangements:
▪️Linear genome: Most DNA viruses have linear genomes, where the DNA molecule is a straight line.
▪️Circular genome: Some DNA viruses, such as the Papillomaviridae, Polyomaviridae (supercoiled), and Hepadnaviridae (incomplete), have circular genomes. The DNA forms a closed loop, like a circle.
🔸RNA Viruses:
RNA viruses have genomes made up of RNA molecules. Similar to DNA viruses, RNA viruses can have different types of RNA genomes: Double-stranded RNA (dsRNA) and Single-stranded RNA (ssRNA).
- Double-stranded RNA genomes (dsRNA): The Reoviridae family of viruses has dsRNA genomes. It means that the viral genome consists of two RNA strands that are complementary to each other.
- Single-stranded RNA genomes (ssRNA): Most RNA viruses have ssRNA genomes. They can be further classified into Positive-sense RNA (+ssRNA) and Negative-sense RNA (-ssRNA) based on the orientation and polarity of the RNA strand.
- Positive-sense RNA viruses (+ssRNA): Examples of +ssRNA viruses include Retroviridae, Togaviridae, Flaviviridae, Coronaviridae, Hepeviridae, Caliciviridae, and Picornaviridae. The RNA strand of these viruses can be directly translated by the host cell’s machinery to produce viral proteins.
- Negative-sense RNA viruses (-ssRNA): Examples of -ssRNA viruses include Arenaviridae, Bunyaviridae, Paramyxoviridae, Orthomyxoviridae, Filoviridae, and Rhabdoviridae. The RNA strand of these viruses serves as a template for the production of complementary RNA strands, which are then used for translation.
Like DNA genomes, RNA genomes can also have different shapes or arrangements:
▪️Linear genome: Most RNA viruses have linear genomes, similar to linear DNA viruses. The RNA molecule is a straight line.
▪️Circular genome: Some RNA viruses, such as Arenaviridae and Deltaviridae, have circular genomes. The RNA forms a closed loop.
▪️Segmented genomes:
In addition to linear and circular genomes, some RNA viruses have segmented genomes. This is an another category of genome shape besides linear and circular, so Viral genomes can be linear or circular or segmented but not circular segmented. Segmented RNA viruses have their genome divided into multiple distinct RNA segments. This arrangement allows for the exchange of genome segments between different strains of the virus during co-infection of a single host cell. This process is known as viral reassortment and can lead to the emergence of new viral variants.
Examples of segmented RNA viruses include:
- Bunyavirus: Bunyaviruses have genomes composed of three segments.
- Orthomyxovirus: Orthomyxoviruses, such as influenza viruses, have genomes composed of eight segments.
- Arenavirus: Arenaviruses have genomes divided into two segments.
- Reovirus: Reoviruses have genomes composed of 10 to 12 segments.
Explain Capsid and it’s different types:
The capsid is a key component of a virus and refers to the protein coat that encloses the viral genome. It plays a crucial role in protecting the viral genetic material and facilitating virus replication and infection. The capsid is made up of smaller protein subunits called capsomeres, which assemble together to form the overall structure.
The structure of the capsid can vary depending on the type of virus. There are two main types of capsid structures: helical and icosahedral.
- Helical capsid structure: This structure is typically found in Enveloped viruses. Enveloped viruses have an outer lipid membrane layer that surrounds the capsid. The helical capsid consists of protein subunits arranged in a helical pattern around the viral genome. The capsid proteins interact with the viral RNA or DNA, forming a spiral-shaped structure. Examples of viruses with helical capsids include the influenza virus and the measles virus.
- Icosahedral capsid structure: This structure is found in both Enveloped viruses and Non-enveloped viruses. Nonenveloped viruses lack an outer lipid membrane layer and rely solely on the capsid for protection. Enveloped viruses have both a capsid and an outer lipid envelope. The icosahedral capsid is composed of capsomeres arranged in a symmetrical icosahedral shape. An icosahedron is a geometric shape with 20 triangular faces, 12 vertices, and 30 edges. Most DNA viruses have icosahedral capsids, with the exception of the poxvirus, which has a more complex capsid structure. Examples of viruses with icosahedral capsids include the adenovirus and the herpesvirus.
The icosahedral capsid structure is highly efficient in terms of minimizing the amount of protein needed to form a stable shell, while still providing protection to the viral genome. The icosahedral shape allows for maximum symmetry and close packing of the capsomeres, providing stability to the capsid.
It’s important to note that the capsid structure is independent of the type of genetic material (DNA or RNA) present in the virus. Both DNA and RNA viruses can have either helical or icosahedral capsids. The choice of capsid structure is determined by the specific viral species and its evolutionary adaptations.
Helical Capsid is found in ________________
Enveloped viruses only
Icosahedral Capsid is found in ________________
Enveloped viruses and Non-enveloped viruses
Explain Viral Envelope:
🔸Envelope: The envelope is a lipid bilayer that surrounds the capsid of some viruses. It is composed of phospholipids, similar to the lipid bilayers found in cell membranes. The envelope contains viral glycoproteins, which are proteins on the outer surface of the envelope, as well as host cell proteins that may have been acquired during the process of viral assembly or budding.
▪️Origin of the envelope: The envelope of most enveloped viruses is derived from the host cell's plasma membrane when the newly formed virions exit the host cell. As the virus buds from the host cell, it acquires a portion of the cell's membrane, which becomes the viral envelope. However, there are exceptions to this rule. For example, viruses belonging to the Herpesviridae family acquire their primary envelope from the host cell's nuclear membranes rather than the plasma membrane.
▪️Vulnerability to inactivation: The presence of the lipid bilayer in enveloped viruses makes them vulnerable to certain factors that can disrupt or destroy the envelope. Organic solvents (such as alcohol), detergents, and dry heat can rapidly inactivate enveloped viruses by disrupting the lipid bilayer. This vulnerability is in contrast to nonenveloped viruses, which lack a lipid envelope and are generally more resistant to these inactivation methods.
🔸Nonenveloped viruses: Some viruses do not possess an envelope and are referred to as nonenveloped or naked viruses. These viruses consist only of the protein capsid that directly encloses the viral genetic material. Examples of nonenveloped DNA viruses include Papillomaviridae, Adenoviridae, Parvoviridae, and Polyomaviridae. Examples of nonenveloped RNA viruses include Caliciviridae, Picornaviridae, Reoviridae, and Hepeviridae.
Viral Structural Components include:
1- Genetic material (Always present): either DNA or RNA
2- Capsid (Always present): either Helical or Icosahedral
3- Envelope (Optional)
Viral Life Cycle:
- Attachment to the host cell: Viruses have specific proteins on their surfaces that bind to complementary receptor molecules on the surface of host cells. This attachment is crucial for the virus to gain entry into the host cell. The interaction between viral proteins and host cell receptors is highly specific, and different viruses have different receptor preferences. This specificity determines the types of cells that a virus can infect.
- Penetration into the host cell:
a. Nonenveloped viruses: Nonenveloped viruses can enter the host cell through two main mechanisms:- Endocytosis: The host cell engulfs the virus, forming a membrane-bound vesicle called an endosome. The virus is then released into the cytoplasm of the host cell from the endosome.
- Transmembrane transport: Some nonenveloped viruses can directly penetrate the host cell membrane and enter the cytoplasm without being engulfed in a vesicle.
In transmembrane transport, the virus interacts with specific receptors on the host cell surface, which triggers a conformational change in the viral proteins. This conformational change allows the virus to directly penetrate the host cell membrane and enter the cytoplasm.
The exact details of transmembrane transport can vary depending on the specific virus and host cell involved. However, in general, the viral proteins responsible for transmembrane transport undergo structural changes that enable them to interact with and disrupt the host cell membrane. This disruption creates a pore or channel through which the virus can pass, allowing it to enter the host cell’s cytoplasm.
b. Enveloped viruses: Enveloped viruses can enter the host cell through two main mechanisms:
- Endocytosis: Similar to nonenveloped viruses, enveloped viruses can be taken up by the host cell through endocytosis. The viral envelope fuses with the membrane of the endosome, releasing the virus into the cytoplasm.
- Fusion with host cell membrane: Enveloped viruses can also fuse their envelope directly with the host cell’s plasma membrane. This fusion allows the viral contents to enter the host cell without being enclosed in an endosome.
- Uncoating of the nucleic acid: Once inside the host cell, the virus needs to release its genetic material from the protective protein coat called the capsid. Uncoating can occur through various mechanisms depending on the virus type. It can be triggered by changes in pH, enzymatic activity, or other host cell factors. Uncoating exposes the viral genetic material, allowing it to interact with the host cell’s machinery for replication and protein synthesis.
- Replication of the nucleic acid and formation of viral proteins:
a. Transcription: The viral genetic material (DNA or RNA) serves as a template for the synthesis of messenger RNA (mRNA) molecules. This process, known as transcription, involves the production of mRNA molecules that carry the instructions for viral protein synthesis.
b. Translation: The host cell’s ribosomes read the viral mRNA and use it as a blueprint to synthesize viral proteins. The viral proteins are essential for various functions, including shutting down the host cell’s defense mechanisms, replicating the viral genetic material, and forming the structural components of new virus particles. - Assembly of virus components: As the viral proteins are synthesized, they come together with the replicated viral genetic material to form new virus particles, called virions. This assembly process is highly orchestrated and specific to each virus type. The viral genetic material is packaged inside the protective protein capsid, which provides stability and protection to the viral genome.
- Viral release:
a. Enveloped viruses: Enveloped viruses are released from the host cell through a process called budding. During budding, the newly formed virus particle pushes through the host cell’s membrane, acquiring a portion of the membrane as its envelope. The virus is released from the host cell while still surrounded by the host cell’s membrane and its own viral envelope.
b. Nonenveloped viruses: Nonenveloped viruses are released from the host cell through host cell lysis. This process involves the destruction of the host cell membrane, causing it to burst open and release the virus particles.
🔸 Eclipse period: The eclipse period refers to the time between uncoating of the viral genetic material inside the host cell and the production of recognizable virus particles. During this period, the viral components are being synthesized and assembled inside the host cell, but they are not yet organized into fully formed virus particles. This phase is often characterized by high levels of viral replication and protein synthesis.
Which viral family can acquire their primary envelope from host cell nuclear membranes?
Herpesviridae
Name the Enveloped DNA viruses:
Name the Enveloped RNA viruses:
🔸 Caliciviridae
🔸 Picornaviridae
🔸 Reoviridae
🔸 Hepeviridae
All DNA viruses have icosahedral capsid except _______________
Poxvirus, which has a complex capsid
All DNA viruses have _________ capsid, except ____________.
All DNA viruses are icosahedral except poxvirus
Positive-sense RNA viruses (+ssRNA) include which viral families:
🔸 Retroviridae
🔸 Togaviridae
🔸 Flaviviridae
🔸 Coronaviridae
🔸 Hepeviridae
🔸 Caliciviridae
🔸 Picornaviridae
🔺Mnemonic: Imagine a Tiger eating a flaming hot Cheetos and Corn, with a Hippi drinking Corona beer, in an old Classic Retro club.
Tiger = Togaviridae
Flaming = Flaviviridae
Corn = Picornaviridae
Hippi = Hepeviridae
Corona beer = Coronaviridae
Classic = Caliciviridae
Retro = Retroviridae
Negative-sense RNA viruses (-ssRNA) include which viral families:
🔸 Arenaviridae
🔸 Bunyaviridae
🔸 Paramyxoviridae
🔸 Orthomyxoviridae
🔸 Filoviridae
🔸 Rhabdoviridae
Retroviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense single stranded RNA viruses (+ssRNA)
Togaviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense RNA viruses (+ssRNA)
Flaviviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense RNA viruses (+ssRNA)
Coronaviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense RNA viruses (+ssRNA)
Hepeviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense RNA viruses (+ssRNA)
Caliciviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense RNA viruses (+ssRNA)
Picornaviridae are Positive-sense RNA or Negative-sense RNA:
Positive-sense RNA viruses (+ssRNA)
Arenaviridae are Positive-sense RNA or Negative-sense RNA:
Negative-sense RNA viruses (-ssRNA)
Bunyaviridae are Positive-sense RNA or Negative-sense RNA:
Negative-sense RNA viruses (-ssRNA)
Paramyxoviridae are Positive-sense RNA or Negative-sense RNA:
Negative-sense RNA viruses (-ssRNA)
Orthomyxoviridae are Positive-sense RNA or Negative-sense RNA:
Negative-sense RNA viruses (-ssRNA)
Filoviridae are Positive-sense RNA or Negative-sense RNA:
Negative-sense RNA viruses (-ssRNA)
Rhabdoviridae are Positive-sense RNA or Negative-sense RNA:
Negative-sense RNA viruses (-ssRNA)
Most RNA viruses have a Linear genetic material except ___________ and __________ have a Circular genetic material, while other RNA families like _________ , ___________ , ___________ , ____________ have a Segmented genetic material.
🔸Linear: most RNA viruses
🔸Circular: Arenaviridae, Deltaviridae
🔸 Segmented RNA viruses: A segmented genome facilitates the exchange of genome segments between different virus strains during coinfection of a single host cell (i.e., viral reassortment).
Bunyavirus: 3 segments
Orthomyxovirus: 8 segments
Arenavirus: 2 segments
Reovirus: 10–12 segments
RNA viruses with circular genetic material include:
Arenaviridae and Deltaviridae
RNA viruses with segmented genetic material include:
Arenavirus: 2 segments
Bunyavirus: 3 segments
Orthomyxovirus: 8 segments
Reovirus: 10–12 segments
🔺Mnemonic:
For Arenavirus: Imagine in an Olympic arena there are 2 warriors fighting each other.
For Bunyavirus: Imagine the 3 Power Puff girls banat.
For Orthomyxovirus: Imagine the number 8 as Biceps, Biceps equals ortho.
For Reovirus: Imagine Reo means Rio meaning Brazil 🇧🇷 meaning Pele number 10.
Most RNA viruses are Single-stranded RNA except ___________.
Reoviridae which are Double-stranded RNA genomes (dsRNA)
🔺Mnemonic:
Reoviridae = Rio DeJaneiro
The D in DeJaneiro make you remember Double Stranded RNA
Rio Double stranded
Most RNA viruses are Single stranded RNA viruses or Double Stranded RNA viruses:
Single stranded RNA viruses
Most DNA Viruses are Double-stranded DNA genomes (dsDNA) except __________
Parvoviridae which are Single-stranded DNA genomes (ssDNA)
Most DNA viruses are Single stranded DNA viruses or Double stranded DNA viruses:
Double stranded DNA viruses
The shape of RNA viruses can be:
Linear or Circular or Segmented
The shape of DNA viruses can be:
Linear or Circular
Most DNA viruses shape are:
Linear
Which DNA viruses have a circular shape:
Papillomaviridae
Polyomaviridae
Hepadnaviridae
Receptors that different viruses recognize on the host cell surface for entry:
These are receptors found on the surface of target host cells, that certain viruses specifically recognize and interact with their target receptors for entry.
Cytomegalovirus CMV interacts with which host cell surface receptor to gain entry?
Integrins
Cellular integrins function as entry receptors for CMV.
Epstein-Barr Virus EBV interacts with which host cell surface receptor to gain entry to host cells?
CD21
These are receptors found on the surface of target host cells, that EBV specifically recognize and interact with for entry.
Human Immunodeficiency Virus HIV interacts with which host cell surface receptor to gain entry to host cells?
CD4 and CXCR4 and CCR5
HIV requires multiple receptors for entry. The primary receptor is CD4, which binds to the viral envelope protein gp120. Additionally, co-receptors CXCR4 and CCR5 are involved in viral entry into specific cell types.
These are receptors found on the surface of target host cells, that HIV specifically recognize and interact with for entry.
Parvovirus B19 interacts with which host cell surface receptor to gain entry to host cells?
P antigen on erythrocytes
Parvovirus B19 specifically recognizes the P antigen on erythrocytes as its receptor.
Rabies virus interacts with which host cell surface receptor to gain entry to host cells?
Nicotinic acetylcholine receptor
Rabies virus specifically target Nicotinic acetylcholine receptor on host cell for entry.
Rhinovirus interacts with which host cell surface receptor to gain entry to host cells?
Intercellular Adhesion Molecule 1 (ICAM-1)
Rhinovirus attaches to intercellular adhesion molecule 1 (ICAM-1) as its receptor.
🔸Mnemonic: The rhino knocked over mI CAMera”: rhinovirus enters cells via ICAM-1.
SARS-CoV-2 interacts with which host cell surface receptor to gain entry to host cells?
Angiotensin-converting enzyme 2 (ACE2)
These are receptors found on the surface of target host cells, that SARS-CoV-2 specifically recognize and interact with for entry.
What are the mechanisms by which viruses cause infection in the host:
There are several mechanisms by which viruses cause infection in the host:
- Cytolysis:
This mechanism is observed with both:
🔸All Non-enveloped Viruses
🔸Only Some of Enveloped Viruses
During viral replication, the virus takes control of the host cell’s machinery to produce more viral particles. As a result, the host cell becomes overloaded with viral components, leading to its destruction or lysis. This destruction releases the newly formed viruses, which can then go on to infect other cells and propagate the infection further.
- Immunopathological host reactions: In some cases, the host’s immune response against the invading virus can contribute to the pathogenicity. When a virus infects a cell, it can trigger a cellular immune response, particularly involving cytotoxic T cells. These T cells recognize and destroy infected cells to prevent the spread of the virus. However, in certain infections such as hepatitis B virus (HBV), the immune response may cause significant damage to the infected cells and surrounding tissues, leading to tissue inflammation and disease symptoms. It’s important to note that in these cases, the virus itself may not directly cause the destruction of host cells (cytopathogenic), but instead, the immune response plays a major role in tissue damage.
- Transfer of genetic material: Bacteriophages are viruses that specifically infect bacteria. Some bacteriophages possess genes that encode virulence factors, such as exotoxins. When these bacteriophages infect bacteria, they can transfer these virulence factors into the bacterial genome. As a result, the bacteria gain the ability to produce and release these toxins, which can cause damage to the host organism and contribute to the development of disease symptoms.
What are the different courses of a viral infection:
◻️Abortive infection:◻️
In an abortive infection, the virus enters the host’s body but fails to replicate or cause damage to the host cells. This can occur due to various reasons, such as host immune responses effectively eliminating the virus or the virus being unable to hijack the host cell’s machinery for replication. Since the virus does not replicate or cause significant harm, no noticeable symptoms or signs of infection are observed.
◻️Acute infection:◻️
An acute viral infection is characterized by a rapid onset of symptoms and a relatively short duration. When the virus enters the host cells, it hijacks the cellular machinery to replicate and produce new viral particles. The virus damages the infected cells, leading to the release of inflammatory mediators and the activation of the immune system. This immune response, along with the viral replication, causes the manifestation of symptoms such as fever, cough, sore throat, and body aches. Acute infections typically resolve within a few days to a few weeks as the immune system successfully clears the virus from the body.
◻️Chronic infection:◻️
In a chronic viral infection, the virus persists in the host’s body for an extended period, usually more than six months. The virus continues to replicate and cause damage to the infected cells throughout the course of the infection. Chronic infections are often characterized by a persistent immune response, which can lead to ongoing inflammation and tissue damage. Examples of chronic viral infections include chronic hepatitis B and C infections, where the virus can cause liver damage over a long period.
◻️Persistent infection:◻️
A persistent viral infection is a type of infection where the virus continues to replicate and persist within the host’s body for an extended period, often lasting months or even years. Unlike acute infections, which typically resolve within a short period, persistent infections are characterized by the continuous presence of the virus.
In a persistent infection, the virus can either actively replicate or remain relatively dormant but still persist in the body. The interaction between the virus and the host’s immune system plays a crucial role in determining the outcome of the infection.
There are two main types of persistent viral infections:
- Latent infection: In this type of persistent infection, the virus enters a dormant or latent state within the host cells. During latency, the viral genome integrates into the host cell’s DNA or persists as an episome, a separate DNA element within the cell. The viral genes necessary for replication are usually not expressed during this phase, resulting in minimal viral replication and a lack of obvious symptoms.
- Productive Infection: In this type of persistent infection, the virus actively replicates in the host cells and continues to produce new viral particles over time. The immune response tries to control the infection, but the virus can evade or modulate the immune system’s defenses to maintain its presence. This ongoing replication leads to a continuous cycle of viral production and infection.
However, under certain conditions, such as stress, immunosuppression, or other triggers, the latent virus can reactivate and start replicating again. This reactivation leads to the recurrence of infection and the manifestation of symptoms. After reactivation, the virus may undergo another period of latency or continue to replicate, depending on various factors.
Persistent viral infections can have diverse effects on the host. Some individuals may experience ongoing symptoms and complications due to the persistent viral activity, while others may remain asymptomatic or only have intermittent symptoms during periods of viral reactivation.
Examples of viruses that can cause persistent infections include human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and herpesviruses such as herpes simplex virus (HSV) and varicella-zoster virus (VZV).
🔸Latent infection: In a latent viral infection, the virus enters the host cells and remains dormant or inactive for a prolonged period. During latency, the viral genome integrates into the host cell’s DNA or persists as an episome (a separate DNA element) within the cell. The virus does not replicate or cause noticeable symptoms during this phase. However, under certain conditions, such as a weakened immune system or specific triggers, the virus can reactivate and start replicating. This leads to the recurrence of infection and the development of symptoms. Herpesviruses, such as herpes simplex virus (HSV) and varicella-zoster virus (VZV), establish latent infections.
🔸Productive infection:
A productive viral infection refers to a situation where the virus actively replicates within the host cells and produces new viral particles. In this type of infection, the virus is actively engaged in its life cycle, which involves entering the host cells, hijacking the cellular machinery to replicate its genetic material, and assembling new viral particles.
However, in some cases of productive infection, the infected individual may not exhibit significant symptoms or signs of infection, especially in the early stages. This can occur because the virus may replicate at a relatively low level or the immune response may effectively control the infection, preventing the development of noticeable symptoms.
During a productive infection, the virus can still be transmitted to others, even if the infected person does not show obvious signs of illness. This can be a concern, as individuals who are unaware of their infection may unknowingly spread the virus to others.
A common example of a productive infection with few or no signs of infection in the early stages is the human immunodeficiency virus (HIV) infection. After initial transmission, HIV actively replicates within the host cells, particularly immune cells called CD4+ T cells. However, during the early stage of infection, individuals may not experience noticeable symptoms. This can make it challenging to diagnose HIV infection without specific testing. Nonetheless, the virus can still be transmitted to others during this phase.
🔺Transforming infection: Some viruses have the ability to trigger malignant transformation of infected cells, leading to the development of cancer. These viruses may or may not actively replicate within the host cells. Instead, they can interfere with the host cell’s normal growth regulation mechanisms, leading to uncontrolled cell division and tumor formation. Examples include Epstein-Barr virus (EBV), which is associated with certain types of lymphomas, and human papillomavirus (HPV), which is linked to cervical cancer.
What are the types of Persistent Infection:
There are 2 types of Persistent infection: Latent infection and Productive infection
A persistent viral infection is a type of infection where the virus continues to replicate and persist within the host’s body for an extended period, often lasting months or even years. Unlike acute infections, which typically resolve within a short period, persistent infections are characterized by the continuous presence of the virus.
In a persistent infection, the virus can either actively replicate or remain relatively dormant but still persist in the body. The interaction between the virus and the host’s immune system plays a crucial role in determining the outcome of the infection.
There are two main types of persistent viral infections:
🔸Latent infection: In a latent viral infection, the virus enters the host cells and remains dormant or inactive for a prolonged period. During latency, the viral genome integrates into the host cell’s DNA or persists as an episome (a separate DNA element) within the cell. The virus does not replicate or cause noticeable symptoms during this phase. However, under certain conditions, such as a weakened immune system or specific triggers, the virus can reactivate and start replicating. This leads to the recurrence of infection and the development of symptoms. Herpesviruses, such as herpes simplex virus (HSV) and varicella-zoster virus (VZV), establish latent infections.
🔸Productive infection:
A productive viral infection refers to a situation where the virus actively replicates within the host cells and produces new viral particles. In this type of infection, the virus is actively engaged in its life cycle, which involves entering the host cells, hijacking the cellular machinery to replicate its genetic material, and assembling new viral particles.
However, in some cases of productive infection, the infected individual may not exhibit significant symptoms or signs of infection, especially in the early stages. This can occur because the virus may replicate at a relatively low level or the immune response may effectively control the infection, preventing the development of noticeable symptoms.
During a productive infection, the virus can still be transmitted to others, even if the infected person does not show obvious signs of illness. This can be a concern, as individuals who are unaware of their infection may unknowingly spread the virus to others.
A common example of a productive infection with few or no signs of infection in the early stages is the human immunodeficiency virus (HIV) infection. After initial transmission, HIV actively replicates within the host cells, particularly immune cells called CD4+ T cells. However, during the early stage of infection, individuals may not experience noticeable symptoms. This can make it challenging to diagnose HIV infection without specific testing. Nonetheless, the virus can still be transmitted to others during this phase.
Host Defense Mechanisms against Viruses:
RNA interference:
RNA interference (RNAi) is a biological process that regulates gene expression by inhibiting the translation or causing the degradation of specific RNA molecules.
- Production of siRNAs:
- In the context of RNA interference, siRNAs can be generated through exogenous or endogenous processes.
- Exogenous siRNAs: When cells encounter double-stranded RNA (dsRNA) from external sources, such as viral RNA, the dsRNA is recognized by an enzyme called Dicer.
- Endogenous siRNAs: Cells can also produce endogenous siRNAs from their own genes. These genes are transcribed into long double-stranded RNA molecules called precursor siRNAs.
- Processing of siRNAs by Dicer:
- Dicer is an enzyme that plays a crucial role in the RNAi pathway. It recognizes and processes dsRNA molecules, including exogenous dsRNA and precursor siRNAs, into smaller siRNA fragments.
- Dicer cleaves the dsRNA or precursor siRNA into short fragments, typically around 20-25 nucleotides in length. These fragments are the mature siRNAs.
- Assembly of the RNA-induced silencing complex (RISC):
- One of the siRNA strands produced by Dicer is selected and becomes the guide strand within the RISC complex.
- The guide strand is incorporated into the RISC complex, which consists of proteins that help stabilize the siRNA and facilitate its interactions with target RNA molecules.
- Targeting and recognition of RNA molecules:
- The guide strand within the RISC complex binds to complementary sequences on target RNA molecules, primarily messenger RNA (mRNA) molecules.
- The binding occurs through base pairing between the guide strand and the target RNA, allowing the RISC complex to recognize specific mRNA molecules.
- Effects on the targeted RNA molecule:
- Once bound to the target RNA, the RISC complex can exert two main effects:a. Cleavage: In some cases, the RISC complex guides the cleavage of the target RNA at specific positions, leading to its degradation. This prevents the target RNA from being translated into a functional protein.b. Translation inhibition: In other cases, the RISC complex binding to the target RNA hinders its translation into a protein, effectively reducing protein production.
Explain Viral surface proteins:
Viral proteins serve several important functions. The proteins on the surface of the virus mediate the attachment of the virus to specific receptors on the host cell surface. This interaction of the viral proteins with the cell receptor is the major determinant of species and organ specificity. Outer viral proteins are also important antigens that induce neutralizing antibody and activate cytotoxic T cells to kill virus-infected cells. These outer viral proteins not only induce antibodies, but are also the target of antibodies (antibodies bind to these viral proteins and prevent [“neutralize”] the virus from entering the cell and replicating). The outer proteins induce these immune responses following both the natural infection and immunization.
The term “serotype” is used to describe a subcategory of a virus based on its surface antigens. For example, measles virus has one serotype, polioviruses have three serotypes, and rhinoviruses have over 100 serotypes. This is because all measles viruses have only one antigenic determinant on its surface protein that induces neutralizing antibody capable of preventing infection. In contrast, polioviruses have three different antigenic determinants on its surface proteins, ie., poliovirus type 1 has one kind of antigenic determinant, poliovirus type 2 has a different antigenic determinant, and poliovirus type 3 has a different antigenic determinant from types 1 and 2, hence polioviruses have three serotypes. There are two important medical implications of this, one, is that a person can be immune (have antibodies) to poliovirus type 1 and still get the disease, poliomyelitis caused by poliovirus types 2 or 3. The other implication is the polio vaccine must contain all three serotypes in order to be completely protective.
Herpes Simplex Virus Type 1 attaches and interacts with which cell surface receptor of host cells?
Fibroblast Growth Factor Receptor
What triggers the uncoating of the viral capsid?
Low pH within the vesicle degrades the capsid surrounding the genetic material
Explain Viral DNA Genetics and Replication:
◻️ Viruses with DNA genomes (DNA viruses) ◻️
There are 2 important enzymes for DNA viruses replication: DNA-Dependent DNA-Polymerase and DNA-Dependent RNA-Polymerase. Both enzymes are from the host cell.
♦️1- Double Stranded DNA replication:
1)Viral Protein Synthesis
Viruses that have Double stranded DNA genome, have one strand that is positive sense DNA strand and the other is negative sense DNA strand.
The virus will first make viral proteins, DNA-Dependent RNA-Polymerase will synthesize mRNA which is a positive sense strand from the negative sense DNA strand. DNA-Dependent RNA-Polymerase will synthesize a complementary positive sense mRNA from the negative sense DNA strand. The mRNA is then translated to form viral proteins.
2)Viral genome replication:
Double stranded DNA is also replicated by DNA-Dependent DNA-Polymerase, this enzyme will form new double stranded DNAs using the original DNA viral genome. DNA-Dependent DNA-Polymerase will synthesize new positive sense and negative sense DNA strands.
The DNA-Dependent DNA-Polymerase will form new positive sense DNA strand from the original negative sense DNA strand and will form a new negative sense DNA strand from the original positive sense DNA strand. As a result creating a new double stranded DNA for new assembly of Virions.
DNA-Dependent DNA-Polymerase and DNA-Dependent RNA-Polymerase are both enzymes of the host cell that viruses use for replication.
♦️2- Positive Sense Single Stranded DNA replication:
The first step in Positive Sense Single Stranded DNA, is to form a Negative sense DNA strand by DNA-Dependent DNA-Polymerase. So DNA-Dependent DNA-Polymerase will use the original positive sense single DNA strand as a template to synthesize a complementary negative sense DNA single strand which will be the template to synthesize mRNA and copies of the original.
1)Viral Protein Synthesis
The newly formed Negative Sense DNA strand will be used as a template to synthesize a complementary positive sense mRNA. The enzyme that will use this negative sense DNA strand as a template to form mRNA is DNA-Dependent RNA-Polymerase. The mRNA will then be translated to viral proteins.
2)Viral genome replication:
The newly formed Negative Sense DNA strand will also be used as a template by DNA-Dependent DNA-Polymerase to synthesize complementary positive sense DNA strands as to make copies of the original positive sense single DNA strand to make extra viruses.
First Step: Positive Sense Single Stranded DNA enters the cell. DNA-Dependent DNA-Polymerase forms Negative sense Single DNA strand
Second Step: Negative sense Single DNA strand will be used by DNA-Dependent RNA-Polymerase to make positive sense mRNA —> translated to viral proteins
Third Step: Negative sense Single DNA strand will be used as a template to make copies of original genome
—> forming Positive Sense Single DNA Strand
♦️3- Negative Sense Single Stranded DNA replication:
The first step in Negative Sense Single Stranded DNA, is to form a Positive sense DNA strand by DNA-Dependent DNA-Polymerase. So DNA-Dependent DNA-Polymerase will use the original Negative sense single DNA strand as a template to synthesize a complementary Positive sense DNA single strand which will be the template to synthesize copies of the original.
1)Viral Protein Synthesis
The original Negative Sense DNA strand will be used as a template to synthesize a complementary positive sense mRNA. The enzyme that will use this negative sense DNA strand as a template to form mRNA is DNA-Dependent RNA-Polymerase. The mRNA will then be translated to viral proteins.
2)Viral genome replication:
The newly formed Positive Sense DNA strand will be used as a template by DNA-Dependent DNA-Polymerase to synthesize complementary Negative sense DNA strands as to make copies of the original Negative sense single DNA strand to make extra viruses.
First Step: Negative Sense Single Stranded DNA enters the cell. DNA-Dependent DNA-Polymerase forms Positive sense Single DNA strand
Second Step: The original Negative sense Single DNA strand will be used by DNA-Dependent RNA-Polymerase to make positive sense mRNA —> translated to viral proteins
Third Step: The newly formed Positive sense Single DNA strand will be used as a template to make copies of original genome
—> forming Negaitive Sense Single DNA Strand
Explain Viral RNA Genetics and Replication:
◻️ Viruses with RNA genomes (RNA viruses) ◻️
♦️1- Double Stranded RNA Virus replication:
The first step is the entry of the Double Stranded RNA Virus genome into the host cell. The double stranded RNA genome is composed of one positive sense RNA strand and another negative sense RNA strand. The RNA-Dependent RNA-Polymerase is an important enzyme of the virus that will use the original negative sense RNA strand to synthesize a positive sense mRNA for translation and a new positive sense RNA strand which from this new positive sense strand will synthesize a new negative sense RNA strand to make more viral copies.
1)Viral Protein Synthesis
The Double Stranded RNA virus has an enzyme called RNA-Dependent RNA-Polymerase that belongs to the RNA virus itself, it carries this enzyme with it. The RNA-Dependent RNA-Polymerase will use the Negative sense RNA strand as a template to synthesize a positive sense mRNA which will be translated to viral proteins.
2)Viral genome replication:
The RNA-Dependent RNA-Polymerase will also use the original Negative sense RNA strand of the Double stranded RNA virus to synthesize a complementary Positive sense RNA strand. Then the RNA-Dependent RNA-Polymerase will use this Newly synthesized Positive sense RNA strand as a template to synthesize a Negative sense RNA strand. So now the RNA-Dependent RNA-Polymerase has created 2 new complementary strands which can be assembled to form new Virions.
Step 1: RNA-Dependent RNA-Polymerase uses the negative sense RNA strand to synthesize an mRNA which can be translated:
Step 2: RNA-Dependent RNA-Polymerase uses the original negative sense RNA strand of Double stranded RNA virus to synthesize a new positive sense RNA strand. RNA-Dependent RNA-Polymerase uses this new
positive sense RNA strand to synthesize a new negative sense RNA strand.
Step 3: The 2 new Complementary RNA strands are used to make new virions.
♦️2- Negative sense Single Stranded RNA Virus replication:
The Negative sense Single Stranded RNA Virus is composed of a single strand of RNA that is negative sense. The first step of replication involves the entry of
Negative sense Single Stranded RNA Virus into the host cell. These Negative sense Single Stranded RNA Virus carry with them RNA-Dependent RNA-Polymerase. The RNA-Dependent RNA-Polymerase will use this original negative sense single RNA strand as a template to synthesize a positive mRNA for translation and a new positive sense RNA strand from which RNA-Dependent RNA-Polymerase will use this new positive sense RNA strand as a template to synthesize a new negative sense RNA strand to make copies for the formation of new virions.
1)Viral Protein Synthesis
The RNA-Dependent RNA-Polymerase will use the original negative sense RNA strand as a template to synthesize a positive sense mRNA, which will be used for translation to form viral proteins.
2)Viral genome replication:
The RNA-Dependent RNA-Polymerase will also use the original negative sense RNA strand as a template to synthesize a new positive sense RNA strand. Then the RNA-Dependent RNA-Polymerase will use this newly formed positive sense RNA strand as a template to synthesize a new Negative sense RNA strand. This new Negative sense RNA strand will be the copies of the original strand to assemble new virions.
Step 1: Negative sense RNA strand virus enters host cell. RNA-Dependent RNA-Polymerase a viral enzyme, uses the original Negative sense RNA strand to synthesize mRNA to be translated to viral proteins.
Step 2: RNA-Dependent RNA-Polymerase uses the original Negative sense RNA strand as a template to synthesize a new positive sense RNA strand. Then RNA-Dependent RNA-Polymerase uses this new positive sense RNA strand as a template to synthesize a new Negative sense RNA strand.
Step 3: New Negative sense RNA strand are made as copies of original virus strand to be assembled to make new virions.
♦️3- Positive sense Single Stranded RNA Virus replication:
The Positive sense Single Stranded RNA Virus is composed of a single strand of RNA that is positive sense. The first step of replication involves the entry of
Positive sense Single Stranded RNA Virus into the host cell. These Positive sense Single Stranded RNA Virus are already positive sense meaning they act as mRNA and can be immediately translated to viral proteins because they are positive sense and single stranded. They don’t carry RNA-Dependent RNA-Polymerase with them because they don’t need to, so the original Positive sense Single Stranded RNA act as mRNA, and can be translated by ribosomes to viral proteins such as RNA-Dependent RNA-Polymerase. So these type of viruses don’t carry with them RNA-Dependent RNA-Polymerase because once the original positive sense RNA strand enters the host it can act directly as mRNA and produce as much RNA-Dependent RNA-Polymerase as they want. To make more copies of the Positive sense Single Stranded RNA, the new RNA-Dependent RNA-Polymerase that was synthesized from translation will use the original Positive sense RNA strand as a template to synthesize a new Negative sense RNA strand. Then RNA-Dependent RNA-Polymerase will use this new Negative sense RNA strand as a template to synthesize new Positive sense RNA strand. These new Positive sense RNA strands are copies of the original strand and will be used to assemble new virions.
1)Viral Protein Synthesis:
The Positive sense Single Stranded RNA viruses do not have RNA-Dependent RNA-Polymerase but they can make it. After entry to host cells, the Positive sense Single Stranded RNA will be used directly as mRNA as they are positive sense and single stranded. So the Positive sense Single Stranded RNA will act as mRNA and will be translated to different viral proteins such as RNA-Dependent RNA-Polymerase. The mRNA will be translated to new RNA-Dependent RNA-Polymerase and other different viral proteins.
2)Viral genome replication:
The newly formed RNA-Dependent RNA-Polymerase will use the original Positive sense single strand RNA as a template to synthesize New Negative sense single strand RNA. Then the RNA-Dependent RNA-Polymerase will use this newly formed Negative sense single strand RNA as a template to form new Positive sense single strand RNA. These new Positive sense single strand RNA are copies of the original genome and will used to assemble new virions.
Step 1: Original Positive sense single strand RNA are used directly as mRNA to synthesize RNA-Dependent RNA-Polymerase.
Step 2: RNA-Dependent RNA-Polymerase will use the original Positive sense single strand RNA as template to make New Negative sense single strand RNA. Then RNA-Dependent RNA-Polymerase will use the New Negative sense single strand RNA as template to make New Positive sense single strand RNA. These New Positive sense single strand RNA are copies of the original genome which will be used to make new virions.
♦️4- Positive sense Single Stranded RNA Retroviruses replication:
Reverse Transcriptase or RNA-Dependent DNA-Polymerase is a viral enzyme used by Retroviruses to synthesize new complementary negative sense DNA strand using the original positive sense RNA strand as a template.
These are Single stranded RNA viruses that are positive sense and possess an enzyme called Reverse Transcriptase or RNA-Dependent DNA-Polymerase. When Retroviruses which are positive sense single stranded RNA viruses infect a host cell, they will release an important enzyme called Reverse Transcriptase or RNA-Dependent DNA-Polymerase. This enzyme (Reverse Transcriptase) will use the original Positive sense Single Stranded RNA Retroviruses genome as a template to synthesize its complementary negative sense DNA strand. Reverse Transcriptase uses the original Positive sense RNA as a template to synthesize its complementary Negative sense DNA strand. Then the DNA-Dependent DNA-Polymerase of the host cell enzyme will use the Newly formed Negative sense DNA strand to synthesize its complementary Positive sense DNA strand, forming a double stranded DNA molecule. These newly formed DNA strands can be integrated into the host cell’s DNA. So the new viral DNA strands will be integrated into the host cell’s DNA, so it can be part of the host cell genome.
1)Viral Protein Synthesis:
Reverse Transcriptase or RNA-Dependent DNA-Polymerase will use the original positive sense RNA single strand of Retroviruses as a template to synthesize its negative sense DNA complementary strand. This negative sense DNA will be used as a template by DNA-Dependent DNA-Polymerase of the host cell to synthesize a new Positive sense DNA strand. The negative sense and positive sense DNA strands will form a double stranded DNA that will be integrated into the host cell DNA, so it will be part of the DNA. As it is part of the DNA, the viral DNA that is integrated into the host cel DNA will be transcribed into mRNA which is also the same copy as the original positive sense RNA single strand of Retroviruses, the mRNA will be translated into viral proteins.
2)Viral genome replication:
Because the viral DNA is integrated into the host cell’s DNA, when it is transcribed it will form the positive sense RNA single strand of Retroviruses which is a copy of the original strand.
Explain Viral Genome Replication and Genetics (DNA and RNA):
The human DNA is double stranded, composed of 2 DNA strands:
One strand is positive sense and the second strand is complementary to it which is the negative sense strand.
The positive strand is composed of specific base pairs forming specific codons that will form specific amino acids that will form a specific protein but the negative sense strand is complementary to the positive sense strand so it is composed of base pairs that are complementary to the positive sense strand which is different so they will form different codons meaning they will form different amino acids which will form different proteins. The proteins of the positive sense strand are functional proteins while the proteins from the negative sense strand are non-functional proteins.
So when a virus has a Negative sense strand it needs to replicate it so it can make a complementary Positive sense strand so ribosomes can use this strand to make functional proteins, and then viruses need to replicate this Positive sense strand to create a negative sense strand to create a copy of the original viral genome.
So if whenever a virus replicates its genome strand it forms its opposite complementary strand which can be positive sense or negative sense strand depending on the strand being copied.
The mRNA strand is always positive sense because we need it to be positive sense in order to synthesize functional proteins, and mRNA is always synthesized from a negative sense strand.
Once a Virus enters a cell, it has 2 major priorities:
1- To make viral proteins
2- To make copies of viral genome
◻️ Viruses with DNA genomes (DNA viruses) ◻️
There are 2 important enzymes for DNA viruses replication: DNA-Dependent DNA-Polymerase and DNA-Dependent RNA-Polymerase . Both enzymes are from the host cell.
♦️1- Double Stranded DNA Virus replication:
1)Viral Protein Synthesis
Viruses that have Double stranded DNA genome, have one strand that is positive sense DNA strand and the other is negative sense DNA strand.
The virus will first make viral proteins, DNA-Dependent RNA-Polymerase will synthesize mRNA which is a positive sense strand from the negative sense DNA strand. DNA-Dependent RNA-Polymerase will synthesize a complementary positive sense strand which is mRNA from the negative sense DNA strand. The mRNA is then translated to form viral proteins.
2)Viral genome replication:
Double standard DNA is also replicated by DNA-Dependent DNA-Polymerase, this enzyme will form new double stranded DNAs using the original DNA viral genome. DNA-Dependent DNA-Polymerase will synthesize new positive sense and negative sense DNA strands.
DNA-Dependent DNA-Polymerase and DNA-Dependent RNA-Polymerase are both enzymes of the host cell that viruses use for replication.
♦️2- Positive Sense Single Stranded DNA Virus replication:
The first step in Positive Sense Single Stranded DNA, is to form a Negative sense DNA strand by DNA-Dependent DNA-Polymerase. So DNA-Dependent DNA-Polymerase will use the original positive sense single DNA strand as a template to synthesize a complementary negative sense DNA single strand which will be the template to synthesize mRNA and copies of the original.
1)Viral Protein Synthesis
The newly formed Negative Sense DNA strand will be used as a template to synthesize a complementary positive sense mRNA. The enzyme that will use this negative sense DNA strand as a template to form mRNA is DNA-Dependent RNA-Polymerase. The mRNA will then be translated to viral proteins.
2)Viral genome replication:
The newly formed Negative Sense DNA strand will also be used as a template by DNA-Dependent DNA-Polymerase to synthesize complementary positive sense DNA strands as to make copies of the original positive sense single DNA strand to make extra viruses.
First Step: Positive Sense Single Stranded DNA enters the cell. DNA-Dependent DNA-Polymerase forms Negative sense Single DNA strand
Second Step: Negative sense Single DNA strand will be used by DNA-Dependent RNA-Polymerase to make positive sense mRNA —> translated to viral proteins
Third Step: Negative sense Single DNA strand will be used as a template to make copies of original genome
—> forming Positive Sense Single DNA Strand
♦️3- Negative Sense Single Stranded DNA Virus replication:
The first step in Negative Sense Single Stranded DNA, is to form a Positive sense DNA strand by DNA-Dependent DNA-Polymerase. So DNA-Dependent DNA-Polymerase will use the original Negative sense single DNA strand as a template to synthesize a complementary Positive sense DNA single strand which will be the template to synthesize copies of the original.
1)Viral Protein Synthesis
The original Negative Sense DNA strand will be used as a template to synthesize a complementary positive sense mRNA. The enzyme that will use this negative sense DNA strand as a template to form mRNA is DNA-Dependent RNA-Polymerase. The mRNA will then be translated to viral proteins.
2)Viral genome replication:
The newly formed Positive Sense DNA strand will be used as a template by DNA-Dependent DNA-Polymerase to synthesize complementary Negative sense DNA strands as to make copies of the original Negative sense single DNA strand to make extra viruses.
First Step: Negative Sense Single Stranded DNA enters the cell. DNA-Dependent DNA-Polymerase forms Positive sense Single DNA strand
Second Step: The original Negative sense Single DNA strand will be used by DNA-Dependent RNA-Polymerase to make positive sense mRNA —> translated to viral proteins
Third Step: The newly formed Positive sense Single DNA strand will be used as a template to make copies of original genome
—> forming Negaitive Sense Single DNA Strand
◻️ Viruses with RNA genomes (RNA viruses) ◻️
♦️1- Double Stranded RNA Virus replication:
The first step is the entry of the Double Stranded RNA Virus genome into the host cell. The double stranded RNA genome is composed of one positive sense RNA strand and another negative sense RNA strand. The RNA-Dependent RNA-Polymerase is an important enzyme of the virus that will use the original negative sense RNA strand to synthesize a positive sense mRNA for translation and a new positive sense RNA strand which from this new positive sense strand will synthesize a new negative sense RNA strand to make more viral copies.
1)Viral Protein Synthesis
The Double Stranded RNA virus has an enzyme called RNA-Dependent RNA-Polymerase that belongs to the RNA virus itself, it carries this enzyme with it. The RNA-Dependent RNA-Polymerase will use the Negative sense RNA strand as a template to synthesize a positive sense mRNA which will be translated to viral proteins.
2)Viral genome replication:
The RNA-Dependent RNA-Polymerase will also use the original Negative sense RNA strand of the Double stranded RNA virus to synthesize a complementary Positive sense RNA strand. Then the RNA-Dependent RNA-Polymerase will use this Newly synthesized Positive sense RNA strand as a template to synthesize a Negative sense RNA strand. So now the RNA-Dependent RNA-Polymerase has created 2 new complementary strands which can be assembled to form new Virions.
Step 1: RNA-Dependent RNA-Polymerase uses the negative sense RNA strand to synthesize an mRNA which can be translated:
Step 2: RNA-Dependent RNA-Polymerase uses the original negative sense RNA strand of Double stranded RNA virus to synthesize a new positive sense RNA strand. RNA-Dependent RNA-Polymerase uses this new
positive sense RNA strand to synthesize a new negative sense RNA strand.
Step 3: The 2 new Complementary RNA strands are used to make new virions.
♦️2- Negative sense Single Stranded RNA Virus replication:
The Negative sense Single Stranded RNA Virus is composed of a single strand of RNA that is negative sense. The first step of replication involves the entry of
Negative sense Single Stranded RNA Virus into the host cell. These Negative sense Single Stranded RNA Virus carry with them RNA-Dependent RNA-Polymerase. The RNA-Dependent RNA-Polymerase will use this original negative sense single RNA strand as a template to synthesize a positive mRNA for translation and a new positive sense RNA strand from which RNA-Dependent RNA-Polymerase will use this new positive sense RNA strand as a template to synthesize a new negative sense RNA strand to make copies for the formation of new virions.
1)Viral Protein Synthesis
The RNA-Dependent RNA-Polymerase will use the original negative sense RNA strand as a template to synthesize a positive sense mRNA, which will be used for translation to form viral proteins.
2)Viral genome replication:
The RNA-Dependent RNA-Polymerase will also use the original negative sense RNA strand as a template to synthesize a new positive sense RNA strand. Then the RNA-Dependent RNA-Polymerase will use this newly formed positive sense RNA strand as a template to synthesize a new Negative sense RNA strand. This new Negative sense RNA strand will be the copies of the original strand to assemble new virions.
Step 1: Negative sense RNA strand virus enters host cell. RNA-Dependent RNA-Polymerase a viral enzyme, uses the original Negative sense RNA strand to synthesize mRNA to be translated to viral proteins.
Step 2: RNA-Dependent RNA-Polymerase uses the original Negative sense RNA strand as a template to synthesize a new positive sense RNA strand. Then RNA-Dependent RNA-Polymerase uses this new positive sense RNA strand as a template to synthesize a new Negative sense RNA strand.
Step 3: New Negative sense RNA strand are made as copies of original virus strand to be assembled to make new virions.
♦️3- Positive sense Single Stranded RNA Virus replication:
The Positive sense Single Stranded RNA Virus is composed of a single strand of RNA that is positive sense. The first step of replication involves the entry of
Positive sense Single Stranded RNA Virus into the host cell. These Positive sense Single Stranded RNA Virus are already positive sense meaning they act as mRNA and can be immediately translated to viral proteins because they are positive sense and single stranded. They don’t carry RNA-Dependent RNA-Polymerase with them because they don’t need to, so the original Positive sense Single Stranded RNA act as mRNA, and can be translated by ribosomes to viral proteins such as RNA-Dependent RNA-Polymerase. So these type of viruses don’t carry with them RNA-Dependent RNA-Polymerase because once the original positive sense RNA strand enters the host it can act directly as mRNA and produce as much RNA-Dependent RNA-Polymerase as they want. To make more copies of the Positive sense Single Stranded RNA, the new RNA-Dependent RNA-Polymerase that was synthesized from translation will use the original Positive sense RNA strand as a template to synthesize a new Negative sense RNA strand. Then RNA-Dependent RNA-Polymerase will use this new Negative sense RNA strand as a template to synthesize new Positive sense RNA strand. These new Positive sense RNA strands are copies of the original strand and will be used to assemble new virions.
1)Viral Protein Synthesis:
The Positive sense Single Stranded RNA viruses do not have RNA-Dependent RNA-Polymerase but they can make it. After entry to host cells, the Positive sense Single Stranded RNA will be used directly as mRNA as they are positive sense and single stranded. So the Positive sense Single Stranded RNA will act as mRNA and will be translated to different viral proteins such as RNA-Dependent RNA-Polymerase. The mRNA will be translated to new RNA-Dependent RNA-Polymerase and other different viral proteins.
2)Viral genome replication:
The newly formed RNA-Dependent RNA-Polymerase will use the original Positive sense single strand RNA as a template to synthesize New Negative sense single strand RNA. Then the RNA-Dependent RNA-Polymerase will use this newly formed Negative sense single strand RNA as a template to form new Positive sense single strand RNA. These new Positive sense single strand RNA are copies of the original genome and will used to assemble new virions.
Step 1: Original Positive sense single strand RNA are used directly as mRNA to synthesize RNA-Dependent RNA-Polymerase.
Step 2: RNA-Dependent RNA-Polymerase will use the original Positive sense single strand RNA as template to make New Negative sense single strand RNA. Then RNA-Dependent RNA-Polymerase will use the New Negative sense single strand RNA as template to make New Positive sense single strand RNA. These New Positive sense single strand RNA are copies of the original genome which will be used to make new virions.
♦️4- Positive sense Single Stranded RNA Retroviruses replication:
Reverse Transcriptase or RNA-Dependent DNA-Polymerase is a viral enzyme used by Retroviruses to synthesize new complementary negative sense DNA strand using the original positive sense RNA strand as a template.
These are Single stranded RNA viruses that are positive sense and possess an enzyme called Reverse Transcriptase or RNA-Dependent DNA-Polymerase. When Retroviruses which are positive sense single stranded RNA viruses infect a host cell, they will release an important enzyme called Reverse Transcriptase or RNA-Dependent DNA-Polymerase. This enzyme (Reverse Transcriptase) will use the original Positive sense Single Stranded RNA Retroviruses genome as a template to synthesize its complementary negative sense DNA strand. Reverse Transcriptase uses the original Positive sense RNA as a template to synthesize its complementary Negative sense DNA strand. Then the DNA-Dependent DNA-Polymerase of the host cell enzyme will use the Newly formed Negative sense DNA strand to synthesize its complementary Positive sense DNA strand, forming a double stranded DNA molecule. These newly formed DNA strands can be integrated into the host cell’s DNA. So the new viral DNA strands will be integrated into the host cell’s DNA, so it can be part of the host cell genome.
1)Viral Protein Synthesis:
Reverse Transcriptase or RNA-Dependent DNA-Polymerase will use the original positive sense RNA single strand of Retroviruses as a template to synthesize its negative sense DNA complementary strand. This negative sense DNA will be used as a template by DNA-Dependent DNA-Polymerase of the host cell to synthesize a new Positive sense DNA strand. The negative sense and positive sense DNA strands will form a double stranded DNA that will be integrated into the host cell DNA, so it will be part of the DNA. As it is part of the DNA, the viral DNA that is integrated into the host cel DNA will be transcribed into mRNA which is also the same copy as the original positive sense RNA single strand of Retroviruses, the mRNA will be translated into viral proteins.
2)Viral genome replication:
Because the viral DNA is integrated into the host cell’s DNA, when it is transcribed it will form the positive sense RNA single strand of Retroviruses which is a copy of the original strand.
Explain Recombination in Viral Genetic Diversification:
Viral recombination is a process in which two different viruses exchange genetic material, resulting in offspring viruses that have a combination of genetic traits from both parent viruses.
Imagine there are two viruses, Virus A and Virus B, infecting the same host cell. Each virus has its own unique genetic material, which is stored in its genome. During co-infection, their genomes are present within the host cell.
Inside the host cell, the viruses replicate and produce new viral particles. Sometimes, certain enzymes or proteins in the cell can recognize regions of similarity between the genomes of Virus A and Virus B. These regions are called homologous sequences.
When the enzymes recognize these homologous sequences, they can initiate a process called crossover. Crossover involves breaking and rejoining DNA strands at the homologous regions of the viral genomes.
As a result of the crossover event, genetic material is exchanged between Virus A and Virus B. The offspring viruses that are produced from this recombination carry a combination of genetic material from both parent viruses.
This genetic exchange through recombination can lead to the creation of new viral strains that have unique combinations of genetic traits. It can contribute to the genetic diversity and evolution of viruses, allowing them to adapt to new environments or overcome host defenses more effectively.
Enveloped viruses can enter the host cell by:
- Endocytosis
- Fusion with the host cell membrane
Non-enveloped viruses can enter the host cell by:
- Endocytosis
- Transmembrane transport
Explain Reassortment of Viral Genetic Diversification:
Reassortment causes Antigenic Shift
Viruses with segmented genomes, such as the influenza virus and rotavirus, have a unique genetic structure. Unlike organisms with a single, continuous strand of DNA or RNA, these viruses have their genetic material divided into multiple segments. Each segment contains a portion of the virus’s genetic code. These segments act as independent units and can be reassorted or mixed during certain circumstances.
Reassortment is a genetic process that occurs when two or more viruses of the same strain infect the same host cell. Inside the host cell, the genetic segments of these viruses can mix and exchange with one another. This recombination of genetic material can lead to the creation of offspring viruses with a combination of genetic segments from different parental viruses.
🔸Pathophysiology:
1- Host cell infection: When two or more viruses of the same strain infect the same host cell, a unique opportunity for reassortment arises. Inside the host cell, the genetic segments of these viruses can mix and exchange with one another.
2- Genetic material exchange: During reassortment, the genetic segments from different parental viruses can undergo exchange or recombination. This mixing can result in the creation of offspring viruses that possess a combination of genetic segments from the parental viruses.
3- Emergence of new strains: The offspring viruses generated through reassortment can possess unique genetic compositions that differ from the parental viruses. This genetic diversity can lead to the emergence of new strains with novel characteristics.
One notable example of reassortment is the H1N1 influenza pandemic in 2009. The virus strain responsible for the pandemic, known as H1N1 2009, emerged through reassortment. It was a novel strain that combined genetic segments from human, swine, and avian influenza viruses. This reassortment event resulted in a unique genetic makeup for the H1N1 2009 virus, allowing it to infect humans and spread globally.
Reassortment can have significant consequences, particularly in the context of influenza viruses. One crucial effect is known as antigenic shift. Antigens are proteins on the surface of the virus that are recognized by the immune system. They play a crucial role in determining whether an immune response is mounted against the virus. In the context of reassortment, when two different influenza viruses exchange genetic material, the resulting offspring virus can have a different combination of antigens compared to the parental strains.
This antigenic shift can pose challenges for the immune system. The immune system is highly effective at recognizing and responding to viruses it has encountered before. However, when a reassortment event leads to the emergence of a new strain with different antigens, the immune system may struggle to recognize and mount an effective response against the new strain. This lack of pre-existing immunity can allow the new strain to spread more easily within a population.
The potential consequences of reassortment and antigenic shift are particularly concerning because they can significantly increase the potential of a virus to cause pandemics. A pandemic occurs when a new virus strain spreads globally and causes severe illness in a large number of people. When a reassorted virus strain with novel antigenic properties emerges, the population may have little to no pre-existing immunity to the new strain. This lack of immunity can facilitate the rapid and widespread transmission of the virus, leading to a pandemic.
Explain Complementation of Viral genetic Diversification:
Complementation in viral infections refers to situations where one virus can compensate for the deficiencies or mutations of another virus. There are two scenarios:
🔸Scenario 1: Two Mutated Viruses from the Same or Different Family Infecting the Same Cell:
- In this scenario, two distinct viruses, either from the same viral family or different families, infect the same host cell.
- Each virus carries its own genetic material and may have undergone mutations that result in the loss of certain functions.
-Due to these mutations, both of the viruses have lost or impaired certain functions. These functions can include viral protein production, replication, or other essential processes for the virus’s life cycle.
- However, when both mutated viruses infect the same cell, their genetic material and gene products (proteins) can interact and complement each other’s deficiencies. The key aspect of complementation in this scenario is that the genetic material and gene products (proteins) of the two mutated viruses can interact and complement each other.
- The genetic material of one virus can provide the missing or impaired functions to the other virus, enabling both viruses to collectively carry out the necessary functions for successful replication and infection.
Through this collaboration, the deficiencies of one virus are compensated for by the functional components provided by the other virus. They work together to overcome their individual limitations and establish a successful infection within the host cell.
▪️Example of Scenario 1:
To understand how complementation works, let’s consider an example with two hypothetical viruses: Virus A and Virus B.
Virus A has a mutation that prevents it from producing a vital protein required for its replication. As a result, Virus A, on its own, is unable to complete its life cycle within the host cell.
Virus B, on the other hand, has a mutation that affects its ability to replicate its genetic material. It also cannot complete its life cycle independently.
However, when Virus A and Virus B infect the same cell, something interesting happens. The genetic material and proteins of both viruses interact and complement each other.
Virus A provides the missing protein that Virus B needs for replication, compensating for Virus B’s deficiency. In return, Virus B provides a functional replication machinery that Virus A lacks.
By working together, the two mutated viruses can replicate their genetic material, produce viral proteins, and generate new virus particles, which can then go on to infect other cells and propagate the infection.
🔸Scenario 2: Mutated Viral Genome Codes for a Nonfunctional Protein, while the Nonmutated Viral Genome Codes for a Functional Protein:
- In this scenario, a viral genome undergoes mutation, resulting in the production of a nonfunctional protein.
- However, within the same host cell, there is also another virus with a nonmutated genome that codes for a functional protein.
- The nonmutated viral protein can be utilized by both the mutated and nonmutated viruses to fulfill their respective functions.
- This complementation allows the mutated virus to benefit from the presence of the nonmutated virus and utilize the functional protein it produces.
- An example of Scenario 2 can be seen in hepatitis B virus (HBV) and hepatitis D virus (HDV) co-infection:
1. HBV and HDV: Hepatitis B virus (HBV) and hepatitis D virus (HDV) are two distinct viruses that can cause liver infections.
- HBsAg Production: HBV produces a protein called hepatitis B surface antigen (HBsAg). HBsAg is an envelope protein that surrounds the HBV particles.
- HDV Dependence: HDV is a defective virus that requires an envelope protein to enter host cells and establish an infection. However, HDV cannot produce its own envelope protein.
- Complementation: In this scenario, the complementation occurs when HDV utilizes the HBsAg produced by HBV to complete its life cycle.
- Cooperative Infection: When both HBV and HDV infect the same host cell, HDV takes advantage of the presence of HBsAg produced by HBV.
- Utilizing HBsAg: HDV uses the HBsAg as its envelope protein, allowing it to enter host cells and initiate the infection process.
- Infection Establishment: Without the envelope protein, HDV alone is unable to establish an infection. However, by utilizing HBsAg produced by HBV, HDV complements its deficiency and gains the ability to infect host cells.
- Co-Infection Consequences: Co-infection with HBV and HDV can result in more severe liver disease compared to infection with HBV alone. The presence of HDV can exacerbate liver damage caused by HBV infection.
In summary, complementation in viral infections occurs when two scenarios arise: when two mutated viruses infect the same cell or when a mutated virus benefits from the presence of a nonmutated virus that produces a functional protein. In both cases, the deficient virus is complemented by the functional components of the other virus, allowing for successful viral replication and infection.
Explain Phenotypic Mixing of viral genetic diversification:
Phenotypic mixing, also known as viral phenotypic complementation, occurs when a cell is coinfected with two related viruses, referred to as virus A and virus B. This phenomenon leads to the formation of pseudovirions or viral hybrids.
Here’s a step-by-step breakdown of the process:
Phenotypic mixing, also known as viral phenotypic complementation, is a phenomenon that occurs when a cell is coinfected with two related viruses, typically belonging to the same viral family or sharing similar properties.
- Coinfection: The process starts with the simultaneous infection of a single cell by two different viruses, referred to as virus A and virus B.
- Coating of Virus A: During coinfection, the genetic material (genome) of virus A becomes partially or completely coated by the surface proteins of virus B. This coating occurs due to interactions between the surface proteins of virus B and the genetic material of virus A.
- Pseudovirion Formation: The coating of virus A’s genetic material by virus B’s surface proteins leads to the formation of pseudovirions or viral hybrids. They are called hybrids because they are a mix or sometimes referred to as pseudovirions because they appear as one type due to surface proteins but they are really something else due to different genetic material. These pseudovirions contain the genetic material from virus A and the surface proteins from virus B.
- Genetic Determination: Despite being coated by virus B’s surface proteins, the genetic material of virus A remains intact within the pseudovirions. As a result, when the pseudovirions replicate, the genetic material of virus A determines the genetic makeup of the progeny viruses. This means that the offspring virions produced from the pseudovirions will carry the genetic material of virus A.
- Host Tropism Determination: The surface proteins derived from virus B, which are incorporated into the pseudovirions, play a crucial role in determining the host tropism or infectivity of the hybrid virus. These surface proteins enable the hybrid virus to recognize and infect specific host cells that virus A alone may not be able to target. The surface proteins from virus B contribute to the infectivity and cell specificity of the hybrid virus. Meaning that the genetic material of the pseudovirions belong to a certain strain but their surface proteins belong to a different strain, and these surface proteins will determine which cell they will infect regardless of their different genetic material. This explains why these pseudovirions have the same genetic material of one group but the infectivity of an another group.
- Temporary Nature of Phenotypic Mixing: It’s important to note that phenotypic mixing is typically a temporary phenomenon. As subsequent generations of virions are produced, the pseudovirions gradually lose their infectivity and return to their previous state. The majority of the virions in later generations will predominantly have the surface proteins derived from virus A, resembling the original virus A. This occurs because the genetic material of virus A determines the genetic makeup of the progeny viruses, while the surface proteins from virus B are gradually lost during replication.
In summary, phenotypic mixing occurs when a cell is coinfected with two related viruses, resulting in the formation of pseudovirions. The genetic material of virus A is coated by the surface proteins of virus B, leading to the incorporation of these surface proteins into the pseudovirions. The genetic material of virus A determines the genetic makeup of the progeny viruses, while the surface proteins from virus B contribute to the host tropism and infectivity of the hybrid virus. However, the temporary nature of phenotypic mixing means that subsequent generations of virions gradually lose the surface proteins from virus B and return to the original state of virus A.
Explain Phenotypic masking of Viral genetic diversification:
Phenotypic masking, or transcapsidation, is a phenomenon that occurs when two related viruses infect the same cell and the capsid (the protein coat that surrounds the viral genome) of one virus envelopes the genetic material of another virus. This process leads to the formation of hybrid virions with the capsid of one virus and the genome of another virus.
Here’s a step-by-step breakdown of the process:
- Coinfection by Related Viruses: Phenotypic masking occurs when a single cell is infected by two related viruses, typically belonging to the same viral family or sharing similar properties.
- Capsid Enveloping the Genetic Material: During coinfection, the capsid of one virus envelopes the genetic material (genome) of the other virus. This means that the protein coat of one virus surrounds and protects the genetic material of the other virus.
- Formation of Hybrid Virions: The result of this process is the formation of hybrid virions, which have the capsid of one virus and the genome of another virus. The capsid determines the physical characteristics and stability of the virion, while the genome contains the genetic information necessary for viral replication and production of viral proteins.
- Phenotypic Characteristics: The hybrid virions exhibit phenotypic characteristics determined by the capsid of the virus that envelopes the genetic material. This means that the physical appearance and functional properties of the hybrid virions are primarily influenced by the capsid-derived from one virus.
- Genetic Determination: Despite being enveloped by the capsid of another virus, the genetic material of the virus being masked remains intact within the hybrid virions. As a result, when the hybrid virions replicate, the genetic material determines the genetic makeup of the progeny viruses. This means that the offspring virions produced from the hybrid virions will carry the genetic material of the masked virus.
- Loss of Capsid Proteins: Over time, as subsequent generations of virions are produced, the hybrid virions may lose the capsid proteins derived from the masking virus. This can occur through various mechanisms, including degradation or replacement by the capsid proteins of the masked virus.
In summary, phenotypic masking, or transcapsidation, occurs when two related viruses infect the same cell, and the capsid of one virus envelopes the genetic material of the other virus. This leads to the formation of hybrid virions with the capsid of one virus and the genome of another virus. The hybrid virions exhibit phenotypic characteristics primarily determined by the capsid-derived from one virus. However, the genetic material of the masked virus determines the genetic makeup of the progeny viruses. Over time, the hybrid virions may lose the capsid proteins derived from the masking virus.
What is the difference between Phenotypic Mixing and Phenotypic Masking?
The are several differences between Phenotypic Mixing and Phenotypic Masking.
Phenotypic Mixing as the name implies involves the mixing of Virus A genetic material with Virus B surface proteins, although the key feature of Phenotypic Mixing is that the surface proteins of the hybrid virus will determine its infectivity since the surface proteins will interact and attach to certain receptors on the surface of host cells even though their genetic material belongs to another strain. So imagine a virus having a genetic material like their original strain but it’s infectivity is different due to another viral surface proteins. In Phenotypic mixing the hybrid virus has the genetic material and capsid of Virus A (Genetic material + capsid of one virus) but the surface protein of Virus B.
Phenotypic Masking as the name implies involves the masking of the genetic material by an another viral capsid. When Virus A and Virus B infect the same cell, the genetic material of Virus A is masked by the capsid of Virus B forming a hybrid virus. But this hybrid virus has the genetic material and surface proteins of Virus A but the Capsid of Virus B.
The only different component in a Virus of Phenotypic mixing is the surface protein of an another virus which can give the virus a different infectivity pattern. The only different component in a virus of Phenotypic masking is the acquired capsid, which can give a different structure to the new hybrid virions.
Both Phenotypic Mixing and Phenotypic Masking will produce temporary Hybrid Virions, which with replication will produce viral progeny of the genetic material. Meaning that with replication the acquired surface proteins from Phenotypic mixing and the acquired Capsid from Phenotypic masking will change due to the production of new proteins from the genetic material that the Hybrid Virions carry.
Explain Point Mutations in Viral genetic diversification:
Point mutations refer to small changes or substitutions that occur in the genetic material (DNA or RNA) of an organism. In the context of viruses, point mutations can occur in specific genes, such as the hemagglutinin or neuraminidase genes.
Hemagglutinin (HA) and neuraminidase (NA) are proteins found on the surface of influenza viruses. They play crucial roles in the infection and spread of the virus. Hemagglutinin helps the virus attach to and enter host cells, while neuraminidase facilitates the release of newly formed viral particles from infected cells.
When point mutations happen in the genes encoding hemagglutinin or neuraminidase, they can result in changes to the structure or function of these proteins. These changes can have important implications for the virus.
One significant consequence of point mutations in hemagglutinin or neuraminidase genes is the phenomenon known as antigenic drift. Antigenic drift refers to gradual changes in the surface proteins of a virus over time. These changes can lead to the virus becoming antigenically distinct from previous strains.
Antigens are molecules that can trigger an immune response in the body. In the case of influenza viruses, the immune system recognizes and produces antibodies against specific antigenic sites on the surface proteins, particularly hemagglutinin. These antibodies help to neutralize the virus and protect against future infections.
However, when point mutations occur in the hemagglutinin or neuraminidase genes, the resulting changes in the viral proteins can alter the antigenic sites. As a result, the antibodies produced against previous strains of the virus may no longer be as effective in neutralizing the mutated strains.
This reduced effectiveness of existing antibodies against mutated strains of the virus can increase the potential of the virus to cause epidemics. The population’s immunity, which may have been acquired through previous infections or vaccinations, may not provide full protection against the drifted strains. This can allow the mutated virus to spread more easily and cause more severe illness in susceptible individuals.
It’s important to note that antigenic drift is a gradual process that occurs over time. It is one of the reasons why new flu vaccines need to be developed and administered regularly to provide protection against the most recent circulating strains of the influenza virus.
In summary, point mutations in the hemagglutinin or neuraminidase genes of a virus can lead to antigenic drift. This process involves changes in the surface proteins of the virus, making it more antigenically distinct from previous strains. The altered viral proteins may evade the immune response generated by previous infections or vaccinations, increasing the virus’s potential to cause epidemics.
What Is Viral Genetic Diversification and what are the mechanisms of Viral Genetic Diversification?
Viral genetic diversification refers to the process by which viruses accumulate genetic variations or changes in their genetic material over time.
Through genetic diversification, viruses can generate different forms or strains that may have distinct characteristics compared to the original or parental virus. These changes can impact various aspects of the virus, including its ability to replicate, infect host cells, evade the immune system, and cause disease.
Viral genetic diversification is an essential aspect of viral evolution and plays a significant role in the emergence of new viral strains or even entirely new viral species. It allows viruses to adapt to changing environments, exploit new host species, and overcome host immune responses. The accumulation of genetic variations contributes to the diversity and complexity of the viral world.
It is the result of different mechanisms, such as:
1- Recombination
2- Reassortment
3- Complementation
4- Phenotypic Mixing
5- Phenotypic Masking
6- Point Mutations
Explain Viral hemagglutination inhibition (HAI) test:
The HAI test is a laboratory technique used to detect the presence of specific antibodies in a person’s blood that can neutralize or inhibit the activity of a virus. It is commonly used to diagnose viral infections such as influenza, mumps, and measles.
HAI test step by step:
- Collecting the patient’s blood sample: A small amount of blood, known as serum, is collected from the patient. Serum is the liquid portion of the blood that remains after removing the blood cells and clotting factors. It contains antibodies produced by the immune system in response to previous viral infections or vaccinations.
- Preparing the virus: The virus being tested is prepared for the HAI test. This involves growing the virus in a laboratory setting and inactivating its ability to cause infection. Inactivation ensures that the virus cannot replicate or cause harm when used in the test.
- Mixing the serum and the virus: In the laboratory, the prepared virus and the patient’s serum are mixed together in a controlled environment. The serum contains antibodies that may be specific to the virus being tested.
- Adding red blood cells:
Red blood cells (RBCs) do not naturally have hemagglutinin on their surface. Hemagglutinin is a protein found on the surface of certain viruses, particularly those that cause hemagglutination, such as influenza viruses.
In the viral hemagglutination inhibition (HAI) test, RBCs from a specific animal species, such as chickens or guinea pigs, are used. These RBCs are not naturally coated with hemagglutinin. Instead, they are typically treated with a solution containing purified hemagglutinin from the specific virus being tested.
The purpose of coating the RBCs with hemagglutinin is to mimic the natural interaction between the virus and RBCs. The hemagglutinin on the RBCs acts as a receptor for the virus, allowing the virus to attach to and agglutinate (clump together) the RBCs.
When the patient’s serum, which contains antibodies specific to the virus, is added to the mixture of virus and coated RBCs, the antibodies can bind to the hemagglutinin on the virus particles. This antibody-virus interaction prevents the virus from attaching to the hemagglutinin on the RBCs, thereby inhibiting hemagglutination. The absence of visible clumping indicates that the patient’s serum contains antibodies that can neutralize the virus.
- Observing for hemagglutination: Hemagglutination refers to the clumping or agglutination of red blood cells caused by the virus. When the virus is mixed with the red blood cells, it can cause the cells to stick together, forming visible clumps.
- Hemagglutination inhibition: If the patient’s serum contains antibodies that can recognize and bind to the virus, they will attach themselves to the hemagglutinin on the surface of the virus particles. This binding prevents the virus from attaching to the red blood cells and causing them to clump together. As a result, no visible clumping or agglutination of the red blood cells will occur.
- Determining the titer: The HAI test can be further quantified by performing serial dilutions of the patient’s serum. This means the serum is diluted multiple times, and each dilution is tested for its ability to inhibit hemagglutination. The highest dilution that still shows inhibition of hemagglutination is called the antibody titer. The titer provides information about the concentration or strength of the antibodies in the patient’s serum.
By observing whether the red blood cells clump together or not, the HAI test can determine if the patient’s serum contains antibodies that can neutralize the virus. If the antibodies are present, they will prevent the virus from causing hemagglutination, indicating a positive result for the presence of specific antibodies against the virus.
The HAI test is useful for diagnosing viral infections, determining immune status, and assessing vaccine effectiveness. It provides valuable information about the presence and activity of antibodies in response to viral infections, helping healthcare professionals make accurate diagnoses and guide appropriate treatment decisions.
So some viruses like influenza, mumps, and measles have a surface protein called Hemagglutinin, and the RBCs used in the test are coated and treated with this same surface protein Hemagglutinin, when viruses with Hemagglutinin are mixed with these RBCs coated Hemagglutinin this will result in clumping or agglutination, because the viruses surface proteins Hemagglutinin will bind and stick to the Hemagglutinin of the RBCs, this will cause the viruses and the RBCs in the sample to stick and clump to each other.
But if antibodies specific to the virus Hemagglutinin from the patient’s serum are mixed with the virus and RBC, these antibodies will bind to the virus Hemagglutinin and will neutralize and block these viral
Hemagglutinin as a result preventing clumping or agglutination since the viral Hemagglutinin are blocked.
Explain ELISA (Enzyme-Linked Immunosorbent Assay):
▪️ ELISA (Enzyme-Linked Immunosorbent Assay):
ELISA is a widely used laboratory technique for detecting and quantifying specific proteins or antibodies in a sample. Here’s a step-by-step breakdown of the process:
- Coating: A solid surface, such as a microplate, is coated with the target or known antigen or antibody. This can be done by directly immobilizing the antigen or by using a capture antibody that specifically binds to the antigen.
- Blocking: The coated surface is treated with a blocking agent, such as BSA or milk, to prevent non-specific binding of other proteins in the sample.
- Incubation: The sample, which may contain the unknown or the tested antigen or antibody, is added to the coated surface and allowed to incubate. If the unknown/tested antigen or antibody is present in the sample, it will bind to the immobilized antigen or antibody on the surface.
- Washing: After incubation, the plate is washed to remove any unbound substances and reduce background noise.
- Detection: A detection/known antibody is added to the plate. This detection/known antibody is specific to a different epitope on the unknown/tested antigen or antibody compared to the immobilized antigen or antibody. The detection/known antibody is typically conjugated to an enzyme, such as horseradish peroxidase (HRP).
- Washing: The plate is washed again to remove any unbound detection antibodies.
- Substrate Reaction: A substrate solution containing a chromogenic or fluorogenic substrate for the enzyme is added to the plate. If the detection antibody is bound to the target antigen or antibody, the enzyme will catalyze a reaction that produces a measurable signal, such as a color change or fluorescent emission.
- Measurement: The intensity of the signal is measured using a spectrophotometer or a fluorometer. The signal’s intensity is directly proportional to the amount of target antigen or antibody present in the sample. By comparing the signal to a standard curve generated using known concentrations of the target, the quantity of the target in the sample can be determined.
ELISA is widely used in various applications, including clinical diagnostics, research, and quality control, due to its sensitivity and specificity in detecting target antigens or antibodies.
Explain Direct Immunofluorescence:
▪️ Direct Immunofluorescence:
Direct immunofluorescence is a technique used to detect and visualize specific antigens or antibodies in a sample using fluorescently labeled antibodies. Here’s a detailed breakdown of the steps involved:
- Sample Preparation: The sample, such as a tissue section or cell culture, is collected and prepared for analysis. This may involve fixing the sample to preserve its structure and antigenicity.
- Incubation: The prepared sample is incubated with a primary/known antibody that specifically recognizes the unknown/tested antigen or antibody. The primary/known antibody is directly conjugated to a fluorescent dye, such as fluorescein isothiocyanate (FITC) or rhodamine.
- Washing: Excess unbound primary antibodies are washed away to remove any non-specific binding.
- Visualization: The sample is examined using a fluorescence microscope equipped with appropriate filters. When excited by the specific wavelength of light corresponding to the fluorescent dye, the bound primary/known antibody emits fluorescence, which can be visualized as a signal. The fluorescence signal indicates the presence and location of the unknown/tested antigen or antibody in the sample.
Direct immunofluorescence allows for the direct visualization of unknown/tested antigens or antibodies within a sample, providing valuable information for diagnostic purposes or research studies, particularly in the detection of infectious diseases or autoimmune disorders.
Explain PCR and qPCR and Viral Load:
PCR and qPCR and Viral Load:
To perform PCR and detect a specific virus, a biological sample that potentially contains the virus needs to be collected. The specific type of sample depends on the virus being targeted and the nature of the infection. Here are some examples of common sample types used for viral detection:
- Respiratory Viruses: For viruses that cause respiratory infections, such as influenza or SARS-CoV-2 (the virus that causes COVID-19), samples can be collected from the respiratory tract. This can involve collecting nasal swabs, throat swabs, or sputum samples.
- Bloodborne Viruses: For viruses that primarily infect the bloodstream, such as HIV or hepatitis C virus (HCV), blood samples are collected. This can be done through venipuncture, where a needle is used to draw blood from a vein.
- Gastrointestinal Viruses: Viruses that cause gastrointestinal infections, like norovirus or rotavirus, can be detected by collecting stool samples from infected individuals.
- Genital Infections: Viruses that cause genital infections, such as human papillomavirus (HPV) or herpes simplex virus (HSV), can be detected by collecting samples from the affected genital areas. This can involve swabs or urine samples.
- Tissue Biopsies: In some cases, when the virus is localized in specific tissues or organs, a biopsy may be performed to collect a small sample of the affected tissue for analysis.
Once the sample is collected, it is processed in the laboratory to extract the viral genetic material (RNA or DNA) from the sample.
The extraction of viral genetic material from a biological sample involves several steps. The specific extraction method chosen depends on the type of virus, the sample type, and the available laboratory resources. Here is a general overview of the viral nucleic acid extraction process:
- Sample Preparation: The collected sample, such as nasal swabs, blood, or tissue, undergoes initial processing to remove any contaminants and prepare it for nucleic acid extraction. This may involve steps like centrifugation to separate cell debris or filtration to remove unwanted particles.
- Lysis: The treated sample is then subjected to a lysis step, where the viral particles or infected cells are disrupted to release the viral genetic material. This can be achieved through various methods, including physical disruption (such as freeze-thaw cycles or sonication) or chemical lysis (using detergents or enzymes).
- Nucleic Acid Binding: Once the viral genetic material is released, it needs to be bound and captured to separate it from other cellular components. Different extraction techniques use various methods for this step, such as using silica-based columns, magnetic beads, or organic solvents.
- Washing: To remove impurities and contaminants, the captured viral nucleic acids are washed with appropriate buffers or solutions to ensure purity and reduce potential PCR inhibitors.
- Elution: The final step involves eluting the purified viral nucleic acids from the binding matrix or beads. Elution typically involves the addition of a specific buffer that enables the released nucleic acids to be collected in a separate tube or well, ready for further analysis.
The extracted viral nucleic acids, whether RNA or DNA, can then be used as the template for subsequent PCR analysis. The extracted genetic material is stable and can be stored at appropriate temperatures until further testing.
After extracting the viral nucleic acids from a biological sample, the next step is typically to perform a specific analysis, such as PCR (Polymerase Chain Reaction), to detect and amplify the viral genetic material.
After extracting the genetic material you will use the PCR to amplify these unknown genetic material, but a key point to remember is that the number or the amount of genetic material that is extracted from a sample is different from one sample to another. That’s why when we amplify the genetic material at the starting of the PCR this what differentiates between one sample and another, because some sample may have few number or little amount of genetic material although other sample might have a lot, the little amount of genetic material requires a lot of amplification to reach the Cycle threshold while the huge amount require little amplifications to reach the Ct.
After extracting the genetic material from the virus, we have specific DNA Primers which are short single stranded pieces that are unique to target specific regions of the genetic material of the virus. There are many versions of different DNA primers, each DNA Primer is designed to target a specific virus. For example the DNA primer used for COVID-19 virus is specific to a unique region in the COVID-19 virus genetic material that is not present in other viral genetic material so when use the COVID-19 virus Specific DNA primer it can actually target only COVID-19 virus and can amplify this specific targeted region. Similarly we have DNA primers specific to influenza virus, to HIV, and others. But the key point is that each DNA primer is designed for a unique specific region of the genetic material of specific virus.
As I mentioned that there are many different DNA Primers that target different viruses, so after extracting the viral genetic material we still don’t know what is the virus, the virus is still unknown, but let’s say we are suspecting that the patient has COVID-19 infection, then after extracting the viral genetic material of the unknown virus we will use DNA primers specific to COVID-19 virus in the lab, if after using the COVID-19 DNA Primer there was amplification of the targeted region of the COVID-19 virus then the unknown virus is COVID-19 virus.
If the specific virus causing the infection is suspected to be COVID-19, then after extracting the viral genetic material, specific DNA primers that target the COVID-19 virus can be used in the laboratory.
The DNA primers that are specific to COVID-19 are designed to bind to unique regions within the genetic material of the virus. These primers are designed based on the known genetic sequence of the COVID-19 virus, particularly regions that are specific to COVID-19 and not found in other viruses.
After setting up the PCR reaction with the COVID-19-specific primers, if there is successful amplification of the targeted region of the COVID-19 virus, it indicates that the unknown virus in the patient’s sample is indeed COVID-19. The amplification indicates the presence of viral genetic material that matches the specific sequence targeted by the COVID-19 primers.
It’s important to note that the PCR test for COVID-19 typically involves multiple sets of primers targeting different regions of the virus’s genome to ensure accurate detection. This approach helps to minimize the chances of false-negative results and increases the reliability of the test.
🔸PCR steps:
1. Primer Design: PCR requires the use of specific primers, short DNA sequences that are designed to bind to complementary sequences on the viral genetic material. These primers flank the target region of the virus that needs to be amplified. Primer design is based on the knowledge of the viral genome and the specific sequences that are unique to the target virus.
- PCR Reaction Setup: The PCR reaction is set up in a laboratory using specialized reagents and equipment. Key components of the PCR reaction mix include:
- Extracted viral nucleic acids: The purified viral genetic material obtained from the extraction process.
- Forward and reverse primers: These are specific primers designed to bind to the target viral sequences.
- DNA polymerase: An enzyme that synthesizes new DNA strands using the viral nucleic acids as a template.
- Nucleotides (dNTPs): The building blocks of DNA that are required for the synthesis of new DNA strands.
- Buffer solution: A solution that provides the necessary pH and ionic conditions for the PCR reaction to occur optimally.
Reverse Transcription: If the virus is RNA-based (like HIV and HCV), an additional step called reverse transcription is performed. Reverse transcriptase enzyme converts the viral RNA into complementary DNA (cDNA), which serves as the template for subsequent PCR amplification.
- PCR Cycling: The PCR reaction goes through a series of temperature cycles, typically consisting of three main steps:
a. Denaturation: The DNA sample containing the target sequence is heated to a high temperature, typically around 94-98°C. This causes the DNA strands to separate, resulting in the denaturation of the double-stranded DNA into single strands.
b. Annealing: The sample is then cooled to a lower temperature, usually around 50-65°C. During this step, short DNA primers (specific to the target sequence) bind to complementary regions on each DNA strand, marking the starting point for DNA replication.
c. Extension (or elongation): The temperature is raised to around 72°C, and a DNA polymerase enzyme synthesizes new DNA strands by extending from the primers. The DNA polymerase adds nucleotides to the growing strands, copying the target DNA sequence.
- PCR Amplification Cycles: The denaturation, annealing, and extension steps are repeated for a specific number of cycles (usually 25-40 cycles) to exponentially amplify the target viral DNA or RNA. Each cycle doubles the number of DNA strands, resulting in a significant amplification of the viral genetic material.
- Analysis of PCR Products:
- Gel Electrophoresis: After the PCR amplification, the products can be analyzed using gel electrophoresis. In this technique, the PCR products are loaded onto a gel matrix and subjected to an electric field. The DNA fragments migrate through the gel, and their sizes can be visualized under ultraviolet (UV) light. This technique helps confirm the presence and approximate size of the amplified viral DNA fragments.
- Real-time PCR (qPCR): In real-time PCR, fluorescent dyes or probes are used, which allow for the detection and quantification of the amplified DNA in real-time. The fluorescence emitted during the amplification process is measured by a specialized instrument, and the data can be used to determine the amount of viral DNA present in the original sample.
🔸Real-time PCR and Viral Load:
Real-Time PCR, or quantitative PCR (qPCR), is a laboratory technique that allows scientists to monitor the amplification of DNA in real-time. It’s like a magnifying glass that helps us see how much DNA is being produced during a process called Polymerase Chain Reaction (PCR).
PCR is a method used to make many copies of a specific DNA sequence. It’s like making photocopies of a page so that you have multiple identical copies. Scientists use PCR to study DNA and perform various experiments.
In Real-Time PCR, we use fluorescence, which is a type of light, to measure the amount of DNA being produced as the PCR reaction is happening in real time. To understand how it works, we need to know about two important components: primers and probes.
Primers are short DNA sequences that are designed to bind to specific regions on the DNA that we want to amplify. They act as starting points for DNA replication, in which DNA polymerase can bind to.
Probes are also short DNA sequences, and they sit close to one of the primers. A probe is like a special marker that helps us keep track of the amplification process in real time. It has a fluorescent dye attached to one end and a quenching dye attached to the other end. (The word quenching means to reduce or limit an excitation state)
The fluorescent dye is like a light bulb, and the quenching dye is like a cap that stops the light from shining. When the probe is intact, the quenching dye blocks the fluorescent dye from emitting light.
At the beginning of the PCR reaction, when there is not much DNA, the fluorescence is too weak to be seen by the camera. It’s like having a very dim light that we can’t detect.
But as the PCR reaction progresses and more DNA is made, the DNA polymerase enzyme copies the DNA, and it reaches the probe region. The DNA polymerase cuts up the probe, separating the fluorescent dye from the quenching dye. This separation allows the fluorescent dye to emit light, like removing the cap from the light bulb. Meaning at the beginning of each cycle of DNA replication the probes will bind to a specific DNA segment and as the DNA polymerase starts adding nucleotides to synthesize the strand, it will eventually reach the region where the probe is bound, the DNA polymerase will break the probe every time it reaches this region creating more fluorescence. With every cycle as the DNA replication restarts unbound probes bind to the DNA and then break and on and on creating more fluorescence with each cycle.
The camera records the emitted light, and we can see it on a computer screen in real-time. The increase in fluorescence tells us that more DNA is being produced.
The power of Real-Time PCR is that it allows us to see when the PCR is doubling the amount of DNA with each cycle without stopping the reaction. This doubling phase is called exponential growth. It’s like the DNA is multiplying rapidly.
In the early cycles of Real-Time PCR, the fluorescence is still very low and difficult to detect. But as the DNA accumulates, the fluorescence becomes detectable over the background. This is when the fluorescence doubles with each cycle, indicating the exponential growth phase. (Background fluorescence refers to the light emitted by fluorescent molecules or substances that are present in a sample or reaction, but are not directly related to the specific DNA being amplified in the PCR reaction.
In Real-Time PCR, background fluorescence can arise from various sources. It can come from impurities in the reaction mixture, such as contaminants or non-specific binding of fluorescent dyes. Additionally, biological samples, such as tissues or bodily fluids, may naturally contain fluorescent molecules that contribute to the background fluorescence. Furthermore, some components used in the PCR reaction, such as buffers or enzymes, can exhibit autofluorescence, generating additional background signal.
During the early cycles of the PCR reaction, when the amount of DNA is low, the fluorescence emitted by the target DNA may be very weak or even undetectable. At this stage, the fluorescence signal is often indistinguishable from the background fluorescence, making it challenging to accurately measure the specific DNA amplification.
As the PCR progresses and more DNA is amplified, the amount of target DNA increases. Eventually, the fluorescence signal from the target DNA becomes stronger and surpasses the background fluorescence, becoming distinguishable from the noise.
To obtain reliable and meaningful data, it is important to set a threshold above the background fluorescence level. This threshold is a predefined value or line that helps determine when the fluorescence signal is considered significant and can be reliably detected. It acts as a cutoff point to identify when the fluorescence is strong enough to be attributed to the target DNA rather than the background noise.
The cycle threshold (Ct) is the cycle number at which the fluorescence signal crosses the threshold. It indicates the point at which the target DNA becomes detectable above the background fluorescence. The Ct value is used to estimate the initial amount of target DNA in the sample, with lower Ct values corresponding to higher initial quantities.
By accounting for background fluorescence and setting an appropriate threshold, scientists can distinguish the true fluorescence signal related to the target DNA from the background noise. This allows for accurate quantification and comparison of the target DNA across different samples
The cycle threshold, or Ct value, is a parameter used in Real-Time PCR to measure the amount of target DNA in a sample. It represents the cycle number at which the fluorescence signal of the target DNA crosses a predefined threshold, indicating that the DNA amplification has reached a detectable level.
During the early cycles of the PCR reaction, the amount of target DNA is low, and the fluorescence signal is weak or undetectable. As the PCR progresses, more copies of the target DNA are produced through DNA amplification. Eventually, the fluorescence emitted by the target DNA becomes strong enough to be reliably detected above the background fluorescence.
The threshold is set at a level above the background fluorescence to ensure that only significant fluorescence signals are considered. When the fluorescence signal from the target DNA exceeds this threshold, it is considered to have crossed the threshold, and the cycle at which this occurs is identified as the Ct value.
A lower Ct value indicates that the target DNA was present at a higher initial quantity in the sample. Conversely, a higher Ct value suggests a lower initial quantity of the target DNA.
The Ct value is useful for comparing the amount of target DNA between different samples or conditions. For example, in disease diagnosis, a higher Ct value for a specific pathogen may indicate a lower level of infection in a patient’s sample.
To accurately determine the exact quantity of target DNA in the sample, a standard curve is often used. The standard curve is created by running PCR reactions with known amounts of the target DNA, covering a range of Ct values. By comparing the Ct value of the unknown sample to the standard curve, the corresponding quantity of the target DNA can be estimated).
As the PCR reaction continues, the amount of DNA keeps increasing, but the rate of increase becomes slower. Eventually, the reaction reaches a plateau where the amount of DNA doesn’t increase much anymore.
To measure the amount of DNA in different samples, we use a threshold line. This line is set above the background fluorescence and during the exponential phase of the PCR. It helps us determine when the fluorescence passes a certain level.
The point at which the fluorescence passes the threshold is called the cycle threshold (Ct) of the PCR. The Ct value is a measure of how much DNA is in the sample. A lower Ct value means a higher amount of DNA.
However, the Ct value doesn’t give us the exact quantity of DNA. It only tells us the relative amount compared to other samples. For example, a sample with a Ct of 10 has more DNA than a sample with a Ct of 11. The difference of two cycles corresponds to four times more DNA, and 20 cycles would be a million times more DNA.
To determine the exact quantity of DNA, we need to compare it to a known amount called a standard. We create a standard curve by running PCR reactions with samples containing known amounts of DNA, covering a range of Ct values. This gives us a reference to estimate the DNA quantity.
Once we know the Ct value of an unknown sample, we can use the standard curve to find the corresponding DNA quantity. It’s like using a map to find the exact location of a place.
So to clear things up, first we will take a sample from any body part that has the unknown offending agent of mind, this sample may have little amount or a lot of pathogens, then we will try to extract the genetic material of these underdetermined number of unknown pathogens. Once the genetic material is extracted we will do PCR, and during the PCR we will add the most likely specific primers that may bind to the most likely unknown pathogen of mind. As I mentioned regarding the sample that was taken, we don’t know the amount of pathogen that may be in that sample, it may be little or a lot. If the the sample contains a lot of this organism then when we amplify this organism, the amplification will generate a lot of copies in few cycles because from the start we have a lot of this organism and copying this organism through PCR amplification will require few cycles to generate a lot copies, on the other hand if the sample contains little amount of this organism then the PCR requires a lot of amplification cycles to generate a lot copies. So if a sample contains a lot of organism it will take few amplification cycles to generate enough copies than if the sample contains few organism which requires a lot of amplification to generate equivalent copies as the high amount organism sample. There is a type of PCR called Quantitative PCR which is a real time PCR used to amplify genetic material samples in real time using fluorescence. The fluorescence is then emitted, which will be detected and drawn on a graph. There is a line of threshold in the graph called Cycle of Threshold. Ct refers to the threshold in which enough DNA amplification has occurred leading to enough fluorescence generation to reach that threshold. If a sample contains a lot of amount of the offending pathogen this causes a lot of the pathogen’s DNA to be extracted, in which when amplified during the qPCR in few cycles enough amplification will occur leading to enough fluorescence to be emitted, as a result reaching the Cycle threshold. But if a sample contains little in amount of the offending pathogen this causes few of the pathogen’s DNA to be extracted, so when amplifying these few extracted DNA it requires a lot of amplification in qPCR to generate enough DNA copies to cause enough fluorescence emission to be recognized by the detector to reach the Cycle Threshold. So if we have 2 samples, Sample A and Sample B. If sample A has high amount of the offending pathogen it requires less amplification to reach Cycle Threshold, but if Sanple B has few amount of the offending pathogen then it requires a lot of amplification cycles to reach Cycle threshold. As a result a sample of high amount of offending organism which gives high amount of extracted DNA requires less amplification cycles to reach Ct but a sample of few organism which gives few extracted DNA requires a lot of amplification cycles to reach Ct.
🔸Standard Curve:
A standard curve in Real-Time PCR is a way to measure and quantify the amount of DNA in a sample. It involves creating a graph that helps you determine the concentration of DNA in an unknown sample based on its Ct value.
To create a standard curve, you start by preparing a series of PCR reactions using known amounts of DNA. These known amounts should cover a range of concentrations. For example, you can prepare PCR reactions with 10, 100, 1000, and 10,000 copies of the target DNA. So you take a known amount of copies of DNA for the initial PCR, so at the beginning of PCR you exactly know how much DNA copies of a specific genetic material is in the PCR to be amplified.
During the PCR process, the instrument measures the amount of known DNA that is being amplified at each cycle. It does this by detecting the fluorescence emitted by special dyes or probes used in the reaction.
The Ct value, or cycle threshold, is the cycle number at which the fluorescence signal reaches a certain level. Lower Ct values indicate higher amounts of DNA in the sample, while higher Ct values indicate lower amounts of DNA.
Now, you plot the known DNA concentrations on the x-axis of a graph and the corresponding Ct values on the y-axis. Each known DNA concentration will have a specific Ct value.
By connecting the plotted points with a line or curve, you create the standard curve. This curve represents the relationship between DNA concentration and Ct values.
When you have an unknown sample and run it through Real-Time PCR, you obtain its Ct value. You then locate this Ct value on the y-axis of the standard curve graph and draw a line to intersect the curve.
From the point of intersection on the curve, draw a horizontal line to the x-axis. The corresponding DNA concentration on the x-axis represents the estimated amount of DNA in the unknown sample.
In summary, a standard curve helps you determine the concentration of DNA in an unknown sample based on its Ct value. By comparing the Ct value to the standard curve, you can estimate the amount of DNA present in the sample.
Real-Time PCR can also be used to amplify and detect more than one DNA target in the same reaction. Each target has a specific probe with a distinct colored dye. These colored dyes help us distinguish between different DNA targets. It’s like using different-colored markers to highlight different things in a picture.
This ability to detect multiple targets in one PCR reaction is useful in various applications, such as diagnosing diseases and conducting medical research.
For example, in a single test, Real-Time PCR can detect the presence of multiple viruses like Influenza A, Influenza B, and SARS-CoV2. Each virus has a specific probe with a different colored dye, allowing us to identify which viruses are present in a sample.
Classification of Enveloped DNA viruses:
There are 3 Families only:
1- Herpesviridae
2- Hepadnaviridae
3- Poxviridae
What is the shape of the capsid of Herpesviridae?
Icosahedral
What type of genetic material do Herpesviridae viruses possess, and what is the shape of their genetic material?
They have a Double Stranded DNA
Linear in shape
Classification of Herpesviridae Family:
There are 8 types of viruses in this family:
🔸 Herpes simplex virus-1 also called Human Herpes Virus 1 (HHV-1)
🔸 Herpes simplex virus-2 also called Human Herpes Virus 2 (HHV-2)
🔸 Varicella-Zoster virus also called Human Herpes Virus 3 (HHV-3)
🔸 Epstein-Barr virus also called Human Herpes Virus 4 (HHV-4)
🔸 Cytomegalovirus also called Human Herpes Virus 5 (HHV-5)
🔸 Human Herpes Virus 6 (HHV-6)
🔸 Human Herpes Virus 7 (HHV-7)
🔸 Human Herpes Virus 8 (HHV-8)
What are the Subfamilies of Herpesviridae:
There are 3 Subfamilies of Herpesviridae:
1- Alpha-Herpesviridae:
🔸 Herpes simplex virus type 1 or Human Herpes Virus 1
🔸Herpes simplex virus type 2 or Human Herpes Virus 2
🔸Varicella zoster virus or Human Herpes Virus 3
2- Beta-Herpesviridae:
🔸Cytomegalovirus or Human Herpes Virus 5
🔸Human herpes viruses 6
🔸Human herpes viruses 7
3- Gamma-Herpesviridae:
🔸Epstein-Barr virus or Human herpes viruses 4
🔸 Human herpes viruses 8
Epstein-Barr virus is also called _________________.
Human Herpes Virus 4
Cytomegalovirus is also called _________________.
Human Herpes Virus 5
Human Herpes Virus 6 can cause:
🔸 Roseola
Roseola, also known as roseola infantum or sixth disease, is a common viral infection that primarily affects infants and young children. Let’s dive into more details about this condition:
Roseola is typically caused by the human herpesvirus 6 (HHV-6) or, less commonly, human herpesvirus 7 (HHV-7). The condition is usually characterized by a high fever that lasts for about 3 to 5 days, followed by the sudden appearance of a rash once the fever subsides.
Here’s a breakdown of the key features of roseola:
- Clinical Presentation:
- High Fever: The illness usually begins with a sudden high fever, often exceeding 103°F (39.4°C). During this period, the child may appear irritable or lethargic.
- Rash: Once the fever resolves, typically after 3 to 5 days, a pinkish-red rash may develop. The rash typically starts on the trunk and spreads to the neck, face, and extremities. It’s important to note that the rash is usually not itchy or bothersome to the child. - Diagnosis:
The diagnosis of roseola is primarily based on clinical presentation. The characteristic pattern of high fever followed by the appearance of a rash helps differentiate it from other childhood rashes. Laboratory testing is not typically required for diagnosis, but it can be performed in certain cases to confirm the presence of HHV-6 or HHV-7. - Management:
There is no specific treatment for roseola since it is a self-limiting viral infection. The focus of management is on relieving symptoms and ensuring the child’s comfort. It is important to monitor the child’s temperature and provide appropriate fever-reducing medications, such as acetaminophen or ibuprofen, as directed by a healthcare professional. Maintaining good hydration is also essential. - Complications:
Roseola is generally a benign condition, and complications are rare. However, in rare cases, the virus can cause febrile seizures (seizures associated with high fever). If your child experiences a seizure or any concerning symptoms, it is crucial to seek medical attention promptly.
Human Herpes Virus 7 can cause:
🔸 Roseola
Roseola, also known as roseola infantum or sixth disease, is a common viral infection that primarily affects infants and young children. Let’s dive into more details about this condition:
Roseola is typically caused by the human herpesvirus 6 (HHV-6) or, less commonly, human herpesvirus 7 (HHV-7). The condition is usually characterized by a high fever that lasts for about 3 to 5 days, followed by the sudden appearance of a rash once the fever subsides.
Here’s a breakdown of the key features of roseola:
- Clinical Presentation:
- High Fever: The illness usually begins with a sudden high fever, often exceeding 103°F (39.4°C). During this period, the child may appear irritable or lethargic.
- Rash: Once the fever resolves, typically after 3 to 5 days, a pinkish-red rash may develop. The rash typically starts on the trunk and spreads to the neck, face, and extremities. It’s important to note that the rash is usually not itchy or bothersome to the child. - Diagnosis:
The diagnosis of roseola is primarily based on clinical presentation. The characteristic pattern of high fever followed by the appearance of a rash helps differentiate it from other childhood rashes. Laboratory testing is not typically required for diagnosis, but it can be performed in certain cases to confirm the presence of HHV-6 or HHV-7. - Management:
There is no specific treatment for roseola since it is a self-limiting viral infection. The focus of management is on relieving symptoms and ensuring the child’s comfort. It is important to monitor the child’s temperature and provide appropriate fever-reducing medications, such as acetaminophen or ibuprofen, as directed by a healthcare professional. Maintaining good hydration is also essential. - Complications:
Roseola is generally a benign condition, and complications are rare. However, in rare cases, the virus can cause febrile seizures (seizures associated with high fever). If your child experiences a seizure or any concerning symptoms, it is crucial to seek medical attention promptly.
Human Herpes Virus 6 and Human Herpes Virus 7 are known to cause ______________.
Roseola
Roseola is caused by which virus:
Human Herpes Virus 6 and Human Herpes Virus 7
Human Herpes Virus 8 can cause:
🔸 Kaposi sarcoma
Kaposi sarcoma is a type of cancer that affects the cells lining blood vessels or lymphatic vessels in the body. It is caused by a virus called human herpesvirus 8 (HHV-8) or Kaposi sarcoma-associated herpesvirus (KSHV). This cancer is most commonly seen in individuals with a weakened immune system, such as those with HIV infection or those who have undergone organ transplantation.
Kaposi sarcoma can appear in different forms, depending on the affected area. The most common types include:
- Classic Kaposi Sarcoma: This form mostly affects elderly individuals of Mediterranean or Eastern European descent. It usually appears as reddish or purplish skin lesions on the lower extremities.
- Endemic African Kaposi Sarcoma: More prevalent in certain regions of Africa, this form primarily affects the lower extremities. It presents as reddish or purple nodules, and lymph nodes may also be involved.
- AIDS-associated Kaposi Sarcoma: This form occurs in individuals with HIV infection. It can affect the skin, mucous membranes, lymph nodes, and internal organs. Lesions can be multiple, vary in color, and may cause symptoms if they involve vital organs.
To diagnose Kaposi sarcoma, doctors typically perform a skin biopsy or biopsy of affected organs. This involves removing a small sample of tissue for examination under a microscope. Additional tests, such as immunohistochemistry or molecular analysis, may be conducted to confirm the presence of HHV-8.
Treatment for Kaposi sarcoma depends on various factors, including the extent of the disease and the individual’s immune status. Options may include antiretroviral therapy (ART) for those with HIV-associated Kaposi sarcoma, local therapies like topical chemotherapy or radiation therapy for limited skin lesions, and systemic therapies such as chemotherapy or targeted therapy for advanced or widespread disease.
The prognosis of Kaposi sarcoma varies depending on the form and stage of the disease. Regular follow-up and monitoring are important to assess the response to treatment and detect any progression.
Classification of Enveloped DNA Viruses:
What type of genetic material do Hepadnaviridae viruses possess, and what is the shape of their genetic material?
The name Hepadnaviridae is derived from liver infectivity and genomic structure: “Hepa” + “DNA”
They have a Partially Double stranded DNA
Circular in shape
What is the capsid shape of Poxviridae viruses?
Complex
What type of genetic material do Poxviridae family possess, and what is the shape of their genetic material?
Double Stranded DNA
Linear in shape
Molluscum contagiosum virus can cause:
🔸 Molluscum contagiosum
Molluscum contagiosum is a common viral skin infection that primarily affects children but can also occur in adults. It is caused by the molluscum contagiosum virus (MCV), a member of the poxvirus family. Let’s dive into more details about this condition:
- Clinical Presentation:
Molluscum contagiosum typically presents as small, raised, firm, and flesh-colored or pearly-white bumps on the skin. These bumps may have a central indentation or “dimple” and are usually painless but can be itchy. They commonly appear in areas that come into direct contact with the virus, such as the face, neck, arms, and hands. In children, the bumps may also be found in the genital area as a result of non-sexual transmission. - Transmission:
The virus spreads through direct skin-to-skin contact with an infected individual or by touching contaminated objects, such as towels or clothing. It can also be transmitted through sexual contact in adults. Molluscum contagiosum is highly contagious, especially in individuals with weakened immune systems. - Diagnosis:
Molluscum contagiosum is usually diagnosed clinically based on the appearance of the characteristic skin lesions. The bumps are unique in their appearance, with a central dimple and a smooth, waxy texture. In some cases, a dermatologist may perform a skin biopsy to confirm the diagnosis. - Management:
In many cases, molluscum contagiosum resolves on its own without treatment, usually within 6 to 12 months. However, treatment options may be considered for cosmetic reasons, prevention of transmission, or if the lesions become bothersome. Treatment options include:
- Physical removal: The bumps can be removed by methods such as cryotherapy (freezing), curettage (scraping), or laser therapy.
- Topical therapy: Creams or ointments containing certain medications, such as imiquimod or tretinoin, can be applied directly to the lesions to promote their resolution.
- Self-care: It is important to avoid scratching or picking at the bumps to prevent spreading the infection to other areas of the body. - Prevention:
To prevent the spread of molluscum contagiosum, it is important to practice good hygiene, avoid direct contact with infected individuals or their personal items, and refrain from sharing towels, clothing, or other personal items. In individuals with weakened immune systems, such as those with HIV infection, prompt diagnosis and management are crucial.
Monkeypox virus can cause:
🔸 Monkeypox
Monkeypox is a rare viral disease that belongs to the same family as smallpox and cowpox. It was first identified in monkeys in Africa in 1958, hence the name “monkeypox.” Let’s delve into more details about this infectious disease:
- Clinical Presentation:
Monkeypox typically starts with flu-like symptoms, including fever, headache, muscle aches, and fatigue. Within a few days, a rash develops, initially as small, raised bumps that progress to fluid-filled blisters. These blisters eventually form crusts and scabs, which then fall off, leaving behind pitted scars. The rash can be widespread and involves the face, trunk, and extremities. Lymph nodes may become swollen and painful. - Transmission:
Monkeypox is primarily transmitted to humans through close contact with infected animals. This can occur through direct contact with bodily fluids, such as blood, respiratory droplets, or by handling infected animals or their bedding. Person-to-person transmission can also occur through respiratory droplets or contact with skin lesions. Human outbreaks are rare but can happen in areas where people live in close proximity to animals. - Diagnosis:
Diagnosing monkeypox requires laboratory testing. A sample of fluid from the skin lesions or respiratory secretions is collected and tested for the presence of the monkeypox virus using methods such as polymerase chain reaction (PCR) or viral culture. - Management:
There is no specific antiviral treatment for monkeypox. Supportive care is provided to relieve symptoms and promote healing. This may include pain relief medications, antipyretics for fever, and keeping the affected areas clean and covered to prevent secondary bacterial infections. In severe cases, hospitalization may be required. - Prevention:
Prevention of monkeypox involves avoiding contact with infected animals or their bodily fluids. Vaccination against smallpox, which provides cross-protection against monkeypox, may be considered in endemic areas or for certain high-risk occupations. Standard infection control measures, such as hand hygiene and use of personal protective equipment, are crucial for healthcare workers involved in the care of monkeypox patients.
It is important to note that monkeypox is a rare disease, and outbreaks are sporadic. The majority of cases reported are in Central and West African countries. Prompt identification, isolation of infected individuals, and implementation of public health measures are vital in controlling the spread of the disease.
Classification of Enveloped DNA Viruses:
There are 3 Enveloped DNA Viruses
♦️Mnemonic: HHP
1) Herpesviridae:
- Herpes simplex virus-1 also called Human Herpes Virus 1 (HHV-1) - Herpes simplex virus-2 also called Human Herpes Virus 2 (HHV-2) - Varicella-Zoster virus also called Human Herpes Virus 3 (HHV-3) - Epstein-Barr virus also called Human Herpes Virus 4 (HHV-4) - Cytomegalovirus also called Human Herpes Virus 5 (HHV-5) - Human Herpes Virus 6 (HHV-6) - Human Herpes Virus 7 (HHV-7) - Human Herpes Virus 8 (HHV-8)
2)Hepadnaviridae:
- Hepatitis B Virus
3) Poxviridae:
🔸Chordopoxvirinae:
🔺Orthopoxvirus Genus:
-Variola Virus
-Cowpox Virus
-Monkeypox Virus
🔺Molluscipoxvirus Genus:
-Molluscum Contagiosum Virus
Classification of Non-Enveloped DNA Viruses:
What is the genetic material of Adenoviridae and what shape does it have?
Double Stranded DNA that is Linear in shape
What is the genetic material of Papillomaviridae and what shape does it have?
Double stranded DNA that is circular in shape.
What is the genetic material of Polyomaviridae and what shape does it have?
Double stranded DNA that is circular in shape.
Which viruses belong to the Papillomaviridae family:
🔸 Human papillomavirus (HPV)
Human papillomavirus (HPV) is a common viral infection that affects both men and women. It is primarily transmitted through sexual contact and can cause various conditions. Let’s delve into the details of HPV:
- Types of HPV:
There are more than 100 types of HPV, and they are classified into high-risk and low-risk types based on their potential to cause cancer. High-risk HPV types, such as HPV types 16 and 18, are associated with an increased risk of developing cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. Low-risk HPV types, such as HPV types 6 and 11, are responsible for causing genital warts. - Transmission:
HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can be spread even if there are no visible signs or symptoms. In some cases, HPV infections can resolve on their own without causing any health problems. However, persistent infections with high-risk HPV types can lead to the development of precancerous or cancerous conditions. - Clinical Presentation:
HPV infections can present in different ways depending on the type and location of the infection:
- Genital Warts: Low-risk HPV types can cause the development of genital warts, which are small, flesh-colored bumps or cauliflower-like growths in the genital area or around the anus.
- Precancerous Lesions: High-risk HPV types can lead to the development of precancerous lesions, such as cervical intraepithelial neoplasia (CIN), anal intraepithelial neoplasia (AIN), or vulvar and vaginal intraepithelial neoplasia. These lesions can progress to cancer if left untreated.
- Cancer: Persistent infection with high-risk HPV types can increase the risk of developing various cancers, including cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These cancers may not have specific early symptoms but can present with abnormal bleeding, pain, or changes in the affected area. - Diagnosis:
The diagnosis of HPV infection can involve various methods:
- Clinical Examination: Visible genital warts can be diagnosed through a physical examination.
- Pap Smear: In women, routine cervical cancer screening with a Pap smear is used to detect abnormal cervical cells that may be caused by HPV infection. If abnormalities are found, further testing, such as HPV DNA testing, may be performed.
- HPV DNA Testing: This test can detect the presence of high-risk HPV types in cervical cells and is often used in conjunction with a Pap smear.
- Biopsy: If a precancerous lesion or cancer is suspected, a biopsy may be performed to obtain a sample of the affected tissue for further examination. - Prevention:
Prevention of HPV infection is crucial and can be achieved through the following measures:
- HPV Vaccination: Vaccines are available to protect against certain high-risk HPV types. These vaccines are recommended for both males and females, typically administered in adolescence before sexual activity begins.
- Safe Sexual Practices: Using condoms consistently and correctly during sexual activity can help reduce the risk of HPV transmission, although they do not provide complete protection.
- Regular Screening: Regular cervical cancer screening with Pap smears, as recommended by healthcare professionals, can help detect early signs of HPV-related abnormalities.
It’s important to note that HPV infections are common, and most individuals who are sexually active will come into contact with HPV at some point in their lives. While many HPV infections resolve on their own without causing significant health problems, regular screening and vaccination are essential in identifying and preventing potential complications.
Which virus is associated with Squamous cell laryngeal carcinoma and Squamous cell pharyngeal cancer:
🔸Human papillomavirus (HPV)
Low-risk subtypes: HPV 1, 2, 6 and 11
High-risk subtypes: HPV 16, 18, 31, and 33
Human papillomavirus (HPV) can cause:
🔸Verruca vulgaris (common warts): especially HPV 1 and 2
🔸Condyloma acuminata: especially HPV 6 and 11
🔸Flat condylomata: especially HPV 16 and 18
🔸Giant condylomata: especially HPV 6 and 11
🔸Malignant transformation (especially infection with high-risk subtypes)
🔺Cervical cancer/CIN (HPV 16 and 18)
🔺Vulvar carcinoma
🔺Vaginal carcinoma
🔺Penile cancer
🔺Anal cancer
🔺Squamous cell laryngeal carcinoma
🔺Squamous cell pharyngeal cancer
- Verruca Vulgaris (Common Warts):
Verruca vulgaris, commonly known as common warts, are caused by HPV infection, specifically HPV types 1 and 2. These warts typically appear as raised, rough-surfaced growths on the skin, often on the hands, fingers, or around the nails. - Condyloma Acuminata:
Condyloma acuminata, also known as genital warts, are caused by HPV infection, particularly HPV types 6 and 11. These warts appear as soft, moist, flesh-colored growths in the genital area, including the penis, vulva, vagina, and anus. - Flat Condylomata:
Flat condylomata are another type of genital warts caused by HPV infection, specifically HPV types 16 and 18. They are characterized by flat, raised, or slightly elevated lesions on the genital mucosa. These HPV types are considered high-risk subtypes because they have a higher potential for malignant transformation. - Giant Condylomata:
Giant condylomata, also known as Buschke-Lowenstein tumors, are rare and locally aggressive lesions caused by HPV infection, primarily HPV types 6 and 11. These tumors appear as large, cauliflower-like growths in the anogenital area. - Malignant Transformation:
▪️Vulvar Carcinoma
▪️Vaginal Carcinoma
▪️Penile cancer
▪️Anal Cancer
▪️Squamous Cell Laryngeal Carcinoma:
Squamous cell laryngeal carcinoma refers to cancer that arises in the cells lining the larynx (voice box). While smoking and alcohol use are the primary risk factors for laryngeal cancer, HPV infection, particularly with high-risk subtypes like HPV types 16 and 18, can also contribute to its development.
▪️Squamous Cell Pharyngeal Cancer:
Squamous cell pharyngeal cancer refers to cancer that arises in the cells lining the pharynx (throat). HPV infection, primarily with high-risk subtypes like HPV types 16 and 18, is increasingly recognized as a cause of pharyngeal cancer, particularly in the oropharynx.
The Polyomaviridae family includes 2 clinically important viruses _____________ and ____________.
🔸 JC virus (JCV)
🔸 BK virus (BKV)
🔸 JC virus (JCV)
The JC virus (JCV) is a type of human polyomavirus that was discovered in 1971. It is named after the initials of the patient, John Cunningham, from whom the virus was first isolated. The JC virus is a small, non-enveloped DNA virus that belongs to the Polyomaviridae family.
In the general population, the JC virus is quite common, with studies indicating that up to 70-90% of adults have been exposed to the virus at some point in their lives. After initial infection, the JC virus usually establishes a latent (inactive) infection in the kidneys and other sites, such as the bone marrow and lymphoid tissue.
In individuals with a healthy immune system, the JC virus typically remains dormant and does not cause any noticeable symptoms or complications. However, in people with weakened immune systems, such as those with HIV/AIDS, organ transplant recipients, or individuals with certain autoimmune conditions, the JC virus can become reactivated and cause significant health problems.
The most notable complication associated with JC virus reactivation is progressive multifocal leukoencephalopathy (PML).
- JC Virus Reactivation:
In individuals with HIV infection, the immune system is compromised, leading to a decreased ability to control viral infections. When the immune system is weakened, the JC virus can reactivate and start replicating in the brain. - Progressive Multifocal Leukoencephalopathy (PML):
PML is a rare but severe neurological condition caused by the JC virus. It primarily affects the white matter of the brain, leading to the destruction of myelin, the protective covering of nerve cells. As a result, individuals with PML can experience a range of neurological symptoms. - Clinical Presentation:
The symptoms of PML can vary depending on the areas of the brain affected. Common signs and symptoms may include:
- Changes in vision, such as blurred vision or loss of visual acuity.
- Difficulty with coordination, balance, and walking.
- Weakness or paralysis on one side of the body.
- Cognitive and behavioral changes, including confusion, memory loss, and personality changes.
- Speech problems.
- Seizures.
- Headache. - Diagnosis:
The diagnosis of PML involves a combination of clinical evaluation and diagnostic tests:
- Neurological Examination: A thorough neurological examination is performed to assess the individual’s symptoms and signs.
- Magnetic Resonance Imaging (MRI): An MRI scan of the brain is typically conducted to detect characteristic white matter lesions that are indicative of PML.
- JC Virus DNA Testing: Cerebrospinal fluid (CSF) samples may be collected and tested for the presence of JC virus DNA using a technique called polymerase chain reaction (PCR). - Management:
There is no specific antiviral treatment for PML, and the main focus is on managing the underlying HIV infection and supporting the individual’s immune system. This may involve the following:
- Antiretroviral Therapy (ART): Effective ART helps to restore the immune system function and control HIV replication, which can slow down the progression of PML.
- Immune Reconstitution Inflammatory Syndrome (IRIS): In some cases, as the immune system starts to recover with ART, an exaggerated inflammatory response can occur, which is known as IRIS. Treatment may involve medications to manage this immune response.
- Supportive Care: Symptomatic treatment is provided to manage specific symptoms and improve the individual’s quality of life. This may include physical therapy, speech therapy, and medications to control seizures or manage pain.
🔸 BK virus (BKV)
The BK virus (BKV) is another member of the polyomavirus family, similar to the JC virus. It was named after the initials of the first patient in whom it was identified, a kidney transplant recipient named BK. Let’s dive into the details of the BK virus:
- Prevalence and Transmission:
The BK virus is widespread in the general population, with up to 80-90% of adults showing evidence of previous infection. Primary infection usually occurs during childhood, and after initial exposure, the virus establishes a latent infection in the kidneys, urinary tract, and other tissues.
The BK virus can be transmitted through various routes, including respiratory droplets, urine, blood transfusions, and organ transplantation. In immunocompetent individuals, the virus remains in a latent state without causing any significant health problems.
- BK Virus and Immunocompromised Individuals:
In individuals with weakened immune systems, such as organ transplant recipients or those with HIV infection, the BK virus can reactivate and cause complications. The immune system plays a crucial role in controlling the replication of the BK virus, so when it becomes compromised, the virus has an opportunity to multiply. - BK Virus-Associated Conditions:
a. BK Virus Nephropathy (BKVN): One of the most significant complications of BK virus reactivation is BKVN, a condition that primarily affects kidney transplant recipients. BKVN occurs when the virus infects the transplanted kidney, leading to inflammation and damage to the kidney tissue. This can result in impaired kidney function and, in severe cases, graft loss.
b. Hemorrhagic Cystitis: BK virus can also cause hemorrhagic cystitis, which is characterized by inflammation and bleeding in the bladder. This condition is commonly seen in hematopoietic stem cell transplant recipients, particularly in the setting of high-dose chemotherapy or radiation therapy.
- Diagnosis:
The diagnosis of BK virus-associated conditions involves a combination of clinical evaluation and laboratory tests:
- Polymerase Chain Reaction (PCR): PCR testing is commonly used to detect the presence of BK virus DNA in urine or blood samples. This test helps confirm active infection or reactivation.
- Histopathological Examination: In cases of suspected BKVN, a kidney biopsy may be performed to examine the kidney tissue for evidence of viral infection and damage. - Management:
Management of BK virus-associated conditions focuses on several key aspects:
- Monitoring: Regular monitoring of BK virus levels in urine or blood can help detect viral reactivation early.
- Reduction of Immunosuppression: In transplant recipients, adjusting immunosuppressive medications to strike a balance between preventing organ rejection and minimizing viral replication is crucial.
- Antiviral Medications: Certain antiviral medications, such as cidofovir and leflunomide, have been used in some cases, but their effectiveness is still being evaluated.
Explain Fifth disease:
Fifth disease, also known as Erythema Infectiosum:
🔸Epidemiology:
Fifth disease is most commonly seen in children, particularly between the ages of 5 and 15 years. Outbreaks of the infection are more common during the winter and spring months. Adults can also be affected, especially those who are in close contact with infected children or have compromised immune systems.
🔸Transmission:
Parvovirus B19, the causative agent of Fifth disease, is primarily transmitted through respiratory droplets. It spreads from person to person through coughing, sneezing, or close contact with an infected individual. The virus can also be transmitted vertically from an infected mother to the fetus during pregnancy.
🔸Incubation Period:
The incubation period for Parvovirus B19 infection is typically 4-14 days, with an average of 10 days. This means that symptoms may appear within this timeframe after exposure to the virus.
Peak Incidence: 5 to 15 years old
🔸Clinical Presentation:
Fifth disease typically begins with a prodromal phase characterized by mild symptoms such as low-grade fever, headache, fatigue, and malaise. After a few days, the characteristic rash appears. It starts with a “slapped cheek” appearance, with bright red erythema on both cheeks, giving the face a flushed appearance. This is followed by a lacy, reticular rash on the trunk and extremities. The rash can be itchy but is usually not painful. The rash tends to fade over time, but it may reappear with heat, exercise, or sun exposure.
▪️Stage 1: Mild Symptoms
Prodromal phase: characterized by mild symptoms such as low-grade fever, headache, fatigue, and malaise.
▪️Stage 2: Exanthem or Rash
It starts 2-5 days after the Mild or Prodromal Phase
The Rash first starts in the face with Slapped check rash and then extends to the trunk and extremities.
Slapped-Cheek Rash: This rash involves the face with diffuse redness of the face with peri-oral sparing.
Rash spread to Trunk and Extremities: Maculopapular rash, may be associated with pruritis in 50% of cases, fades after 7-10 days. Becomes more pronounced after exposure to sunlight or heat.
🔸Diagnosis:
All age groups may have transient normocytic anemia as Parvovirus B19 can affect the RBCs.
▪️Diagnosis in Immunocompetent Children:
🔺Clinical Diagnosis - Slapped Cheek rash
▪️Diagnosis in Immunocompetent Adults:
🔺If diagnosis is unclear we can do serology testing:
IgM antibody
Appears within ∼ 10 days of initial exposure, indicating acute illness
Remains positive for 2–3 months
IgG antibody
Appears approx. 2 weeks following infection
Remains positive for life
▪️Diagnosis in Immunocompromised:
Initial diagnostic test: viral DNA testing such as PCR of blood or bone marrow
Adjunctive diagnostic test: serologic antibody testing
🔸Management:
In most cases, Fifth disease is a self-limiting condition that resolves on its own without specific treatment. Symptomatic management may include rest, hydration, and over-the-counter pain relievers to alleviate any discomfort.
Treatment is not necessary in most cases, as the disease is often self-limited
Analgesics and nonsteroidal anti‑inflammatory drugs (NSAIDs)
Short course of low‑dose prednisone for parvovirus B19‑associated arthritis
🔸Complications:
Fifth disease is generally a mild illness with a low risk of complications. However, certain populations, such as individuals with underlying immune deficiencies or pregnant women, may be at a higher risk of complications. In pregnant women, Parvovirus B19 infection can lead to fetal complications, including hydrops fetalis, as mentioned earlier.
Classification of Pneumoviridae:
Explain Respiratory Syncytial Virus (RSV) and it’s course of Pathogenesis:
Respiratory Syncytial Virus (RSV) is a common viral infection that primarily affects the respiratory tract, particularly in young children. Let’s explore the details of RSV:
🔸Epidemiology:
RSV is a highly prevalent respiratory virus, and almost all individuals have had an RSV infection by the age of 2. Reinfection can occur throughout life due to the presence of different strains and waning immunity over time. This highlights the importance of continued preventive measures, especially in high-risk populations.
RSV infection can cause significant morbidity and mortality, particularly in young children and older adults. In young children, RSV is a leading cause of hospitalization, primarily due to bronchiolitis, which is the inflammation and obstruction of the small airways in the lungs. RSV bronchiolitis can lead to respiratory distress, difficulty breathing, and in severe cases, may require intensive care and mechanical ventilation. In older adults, RSV infection can also lead to severe respiratory illness, especially in those with underlying health conditions.
▪️RSV is the most common cause of hospitalization, bronchiolitis, and pneumonia in infants.
🔸Clinical Presentation:
- Symptoms of Nonspecific Viral Illness:
- Lethargy or fatigue: RSV infection can cause a general feeling of tiredness or lack of energy.
- Irritability: Infants and young children with RSV infection may become more irritable or fussy than usual.
- Decreased appetite: RSV infection can lead to a decreased desire to eat or drink.
- Fever: Fever is a common symptom of RSV infection, although not all individuals will experience it. The fever is usually mild to moderate in nature. - Symptoms of Upper Respiratory Tract Infection:
- Rhinorrhea: RSV infection can cause a runny nose, with the nasal discharge often being thick and copious in infants.
- Acute otitis media: Up to 60% of children with RSV infection may develop acute otitis media, which is an infection of the middle ear. This can present with symptoms such as ear pain, fever, and irritability. - Symptoms of Lower Respiratory Tract Infection:
- Cough: A persistent cough is a common symptom of RSV infection in patients of all ages.
- Tachypnea: RSV infection can lead to rapid breathing, known as tachypnea.
- Rales, wheezes, crackles: These abnormal lung sounds may be heard upon auscultation of the chest. Rales are crackling sounds, wheezes are high-pitched whistling sounds, and crackles are intermittent clicking or rattling sounds.
In Young Children:
- Clinical features of bronchiolitis: RSV infection commonly causes bronchiolitis in infants and young children. Bronchiolitis is characterized by inflammation and narrowing of the small airways in the lungs, resulting in wheezing, difficulty breathing, and respiratory distress.
- Clinical features of pediatric pneumonia: In some cases, RSV infection in young children can progress to pneumonia, which may present with symptoms such as fever, cough, rapid breathing, and signs of respiratory distress.
In Older Children and Adults:
- Clinical features of acute bronchitis: RSV infection in older children and adults may manifest as acute bronchitis, which is characterized by cough, production of sputum, and chest discomfort.
- Clinical features of pneumonia: RSV infection can also lead to pneumonia in older children and adults, with symptoms such as fever, cough, shortness of breath, and signs of pneumonia on clinical examination.
▪️Signs of Severe RSV Infection:
In severe cases of RSV infection, certain signs may indicate respiratory distress or severe illness:
- Signs of respiratory distress: These can include increased work of breathing, such as rapid or labored breathing, retractions (visible inward movement of the chest wall during inhalation), and nasal flaring.
- Hypoxemia: Severe RSV infection may lead to low oxygen levels in the blood, known as hypoxemia.
- Apnea: Episodes of temporary cessation of breathing, known as apnea.
🔸Transmission:
RSV is highly contagious and spreads through respiratory droplets when an infected person coughs or sneezes. It can also be transmitted through direct contact with surfaces contaminated by the virus. RSV is most prevalent during the fall, winter, and spring seasons.
▪️Incubation Period: 2-8 days
🔸Risk Factors:
▪️Risk factors for severe RSV infection in Children:
Age < 6 months: This is considered the single most important risk factor for severe RSV infection in children. Infants under 6 months of age have a higher risk of developing severe lower respiratory tract infection due to their immature immune systems and smaller airways.
Preterm birth, especially if associated with chronic lung disease of prematurity
Congenital heart disease
Immunocompromised states
Neuromuscular disorders that affect the ability to clear airway secretions
Childcare Attendance: Children who attend daycare or are in close contact with other children have a higher risk of RSV infection due to increased exposure to the virus.
Exposure to Tobacco Smoke: Secondhand smoke exposure can impair the respiratory defenses and increase the risk of severe RSV infection in children
▪️Risk factors for severe RSV infection in Adults:
Older age: ≥ 60 years (especially ≥ 75 years)
Chronic lung diseases: COPD, asthma
Cardiac diseases: congestive heart failure, coronary artery disease
Neurologic disorders: cerebrovascular disease, neuromuscular conditions
Diabetes mellitus
Chronic kidney disease
Liver disease
Hematologic disorders
Immunocompromised state
🔸RSV Virulence Factors:
▪️Fusion (F) Protein: The F protein is responsible for viral entry into host cells. It facilitates the fusion of viral and host cell membranes, allowing the virus to enter and infect respiratory epithelial cells. The F protein is a major target for neutralizing antibodies and plays a crucial role in RSV pathogenesis.
▪️Attachment (G) Protein: The G protein is involved in viral attachment to host cells. Although it is not essential for infection, it enhances viral infectivity and contributes to viral replication. The G protein also helps the virus evade the host immune response by interfering with the production of neutralizing antibodies. Glycoprotein G allows the virus to attach to respiratory epithelial cells; its ability to frequently mutate helps the virus evade the host immunity and permits reinfections throughout an individual’s life.
▪️RNA Polymerase: RSV encodes an RNA-dependent RNA polymerase that is crucial for viral replication and transcription of viral genes. This enzyme is essential for the production of viral RNA and proteins necessary for viral replication and assembly.
▪️Nonstructural Proteins: RSV produces nonstructural proteins, such as NS1 and NS2, which play a role in inhibiting the host immune response. These proteins interfere with the production of interferons, which are important antiviral molecules produced by the host cells to limit viral replication.
▪️Interferon Antagonism: RSV has developed mechanisms to counteract the host interferon response, which is a crucial defense mechanism against viral infections. The virus inhibits the production of interferons and interferon-stimulated genes, allowing it to replicate and spread within the host respiratory tract.
🔸Diagnosis:
Routine diagnostic testing for RSV is not usually done, but it can be considered depending on the clinical features. The decision to perform diagnostic testing may be considered by the presence of risk factors for severe RSV infection or the need for hospital admission and infection control measures.
- Additional Studies for Severe Illness: In cases of severe RSV infection, additional studies may be obtained to assess the severity of the illness. These studies can include arterial blood gas (ABG) analysis, respiratory viral panel, and chest x-ray. These tests help evaluate the respiratory status and assist in determining the appropriate management and treatment plan.
- Confirmatory Testing for RSV: If indicated based on clinical suspicion, confirmatory testing for RSV can be performed using various methods:
- Nucleic Acid Amplification Test (reverse transcription PCR): This is the preferred diagnostic method for RSV detection in respiratory tract samples.
- Rapid Antigen Detection Test: This test is primarily used in young children and provides quick results but may have slightly lower sensitivity compared to nucleic acid amplification tests.
- Viral Culture: Although rarely used due to its longer turnaround time, viral culture can also be used to identify RSV.
▪️Chest X-ray Findings: Chest X-ray is not routinely indicated in the diagnosis of RSV infection. However, in cases where a chest X-ray is obtained, it may show nonspecific findings such as peribronchial thickening and pulmonary hyperinflation. These findings are not specific to RSV infection but can be seen in bronchiolitis or pneumonia caused by RSV or other pathogens.
🔸Management:
Management of RSV infection focuses on supportive care to alleviate symptoms and prevent complications. This may include ensuring proper hydration, encouraging rest, using saline nasal drops to relieve nasal congestion, and providing fever-reducing medications if necessary. In severe cases, hospitalization may be required for close monitoring and respiratory support.
▪️Supportive Care:
Cool mist humidifier or steamy showers
Antipyretics for fever and/or discomfort
Encourage adequate fluid intake; if unable to tolerate oral fluids, provide NG/IV fluids.
Gentle nasal suctioning in infants
▪️Pharmacotherapy:
Infants and young children: inhaled ribavirin
🔸Prevention:
Preventing RSV infection is crucial, especially in high-risk individuals. Measures for prevention include frequent handwashing, avoiding close contact with sick individuals, covering the mouth and nose while coughing or sneezing, and disinfecting surfaces regularly. Additionally, for certain high-risk populations, a monthly injection of a monoclonal antibody called palivizumab may be recommended during RSV season for prophylaxis.
🔸Complications:
In infants and young children, RSV infection can lead to more severe respiratory symptoms, such as difficulty breathing, decreased appetite, and dehydration. It may also cause secondary bacterial infections, such as ear infections or pneumonia. In high-risk individuals, RSV infection can sometimes be life-threatening.
Classification of Paramyxoviridae family which belongs under Enveloped RNA viruses:
Explain Measles Pathogenesis:
🔸Epidemiology:
▪️Distribution: Measles tends to occur in regions with low vaccination rates and in resource-limited countries. This is because vaccination against measles has been highly effective in reducing its incidence in countries with widespread immunization programs. However, in areas where vaccination coverage is low or access to healthcare is limited, measles outbreaks can still occur.
▪️Peak Incidence: Measles is most commonly seen in children under 12 months of age. This is because infants in this age group are particularly susceptible to infection due to their immature immune systems and lack of protective antibodies. However, measles can affect individuals of all ages who are not immune to the virus.
▪️Infectivity: Measles is highly contagious, with an infectivity rate of approximately 90%. This means that if an individual with measles comes into contact with 10 susceptible individuals, around 9 of them are likely to become infected. The virus can be transmitted through respiratory droplets when an infected person coughs or sneezes. Importantly, measles is contagious for a period of 4 days before the onset of the characteristic rash (exanthem) and up to 4 days after the rash appears. This makes it possible for the virus to spread even before an individual realizes they are infected.
▪️Risk Factors: Certain individuals are at an increased risk of acquiring or transmitting measles, mumps, and/or rubella. These include:
- Individuals with an immunocompromised state: People with weakened immune systems, such as those with HIV/AIDS or undergoing immunosuppressive therapy, are at higher risk of severe complications if they contract measles. They are also more likely to transmit the virus to others.
- Household or close contacts of immunocompromised individuals: People living or in close contact with individuals who are immunocompromised are at increased risk of acquiring measles and transmitting it to others, especially if they are not immune or have not been vaccinated.
- College students: College campuses, with their close living quarters and frequent social interactions, can facilitate the spread of measles among susceptible individuals who may not have been previously vaccinated or exposed to the virus.
- Health care personnel: Healthcare workers who come into contact with infected individuals are at an increased risk of acquiring measles. This highlights the importance of maintaining up-to-date vaccinations among healthcare professionals to protect both themselves and their patients.
- International travelers: Measles can be imported into countries where the disease is no longer endemic through international travel. Unvaccinated individuals traveling to areas with ongoing measles outbreaks are at risk of acquiring the virus and potentially spreading it to others upon their return.
🔸Etiology
- Pathogen: measles virus (MV), an RNA virus of the Morbillivirus genus belonging to the Paramyxoviridae family
- Route of transmission: direct contact with or inhalation of virus-containing droplets
🔸Clinical Features:
♦️Stage 1 or Prodromal stage, also known as the Catarrhal stage:
Duration: The prodromal stage typically lasts for about 4-7 days [4]. This stage occurs before the onset of the characteristic rash associated with measles.
Presentation: During the prodromal stage, several symptoms and signs can be observed, including:
- Coryza: This refers to a runny or stuffy nose, often accompanied by nasal congestion and sneezing.
- Cough: A persistent cough is commonly seen during this stage.
- Conjunctivitis: Inflammation of the conjunctiva, the thin membrane covering the white part of the eye and inner surface of the eyelids, can cause redness, itching, and discharge.
- Fever: Measles is typically associated with a high fever during the prodromal stage.
Koplik Spots: One of the characteristic findings of measles during the prodromal stage is the presence of Koplik spots. These are pathognomonic enanthem. Koplik spots are tiny white or bluish-gray spots that appear on an irregular erythematous (red) background. They are most commonly found on the buccal mucosa, which is the inner lining of the cheeks. The spots resemble grains of sand and are often described as “salt sprinkled on a wet background”. Koplik spots typically disappear by the second day of the exanthem stage, which is when the rash appears.
The presence of Koplik spots is highly suggestive of measles and can aid in the early diagnosis of the disease. However, it’s important to note that not all individuals with measles will develop Koplik spots, and their absence does not rule out the diagnosis.
♦️Stage 2 or Exanthem Stage:
Duration: The exanthem stage of measles typically lasts for about 7 days and develops 1-2 days after the Koplik spots.
Presentation: During the exanthem stage, several symptoms and signs can be observed, including:
- High fever: Measles is associated with a high fever during the exanthem stage.
- Malaise
Generalized Lymphadenopathy: Measles can cause swelling and tenderness of the lymph nodes throughout the body. This is referred to as generalized lymphadenopathy.
Erythematous Maculopapular Exanthem: The characteristic rash of measles appears during the exanthem stage. It is described as erythematous, meaning it is red, and maculopapular, which means it consists of flat, reddened areas (macules) and raised, small bumps (papules). The rash is blanching, which means it temporarily fades when pressure is applied and then returns when the pressure is released.
Rash Progression: The rash typically starts behind the ears along the hairline and then spreads to the rest of the body, moving downward towards the feet. It is important to note that involvement of the palms and soles is rare in measles.
Rash Resolution: The rash gradually fades after about 5 days from its onset. As it fades, it may leave behind a brown discoloration and desquamation (peeling of the skin) in more severely affected areas.
The presence of the characteristic erythematous maculopapular rash, along with the other symptoms and signs described, is highly suggestive of measles. However, it is important to remember that the diagnosis of measles should be confirmed through appropriate diagnostic testing.
♦️Stage 3 or Recovery Stage:
The cough may persist for another week and may be the last remaining symptom.
🔸Diagnostics
Measles should be suspected in a patient with typical clinical findings, but Laboratory tests are always necessary to confirm the diagnosis.
- CBC: ↓ leukocytes, ↓ platelets
- Serology:
Gold standard: detection of Measles-specific IgM antibodies.
These IgM antibodies appear after the onset of Exanthem. False-Positives may occur with Parvovirus B19 and Rheumatoid Factor.
IgG antibodies
- Identification of pathogen: direct virus detection via reverse-transcriptase polymerase chain reaction (RT-PCR) possible
- Biopsy: affected lymph nodes show paracortical hyperplasia and Warthin-Finkeldey cells (multinucleated giant cells formed by lymphocytic fusion).
🔸Management:
- Symptomatic management
- Vitamin A supplementation: Reduces morbidity and mortality
- Isolate patients with confirmed infection.
- All patients: Isolate for 4 days from the onset of rash (longer if immunocompromised).
- Hospitalized patients: Initiate airborne precautions.
- Measles is a nationally notifiable disease; report all cases to the appropriate health departments within 24 hours.
🔸Complications:
Bacterial superinfection causing:
Otitis media
Pneumonia (most common cause of death)
Laryngotracheitis
Explain Mumps Pathogenesis:
🔸Epidemiology:
Peak age: 5–14 years of age
Sex: ♂ = ♀ for parotitis (however, males are three times more likely to have CNS complications)
🔸Etiology
Mumps is caused by the mumps virus, which belongs to the Paramyxoviridae family. The virus is a single-stranded RNA virus and is the pathogen responsible for mumps infection.
Transmission: Mumps is transmitted from person to person through various means, including:
- Airborne droplets: The virus is primarily transmitted through respiratory droplets when an infected person coughs, sneezes, or talks. These droplets contain the virus and can be inhaled by individuals in close proximity to the infected person.
- Direct contact with contaminated saliva or respiratory secretions: Mumps can also be transmitted through direct contact with infected saliva or respiratory secretions. This can occur through activities such as sharing utensils, kissing, or close personal contact.
Utensils: Utensils, in the context of mumps transmission, refer to objects used for eating or drinking, such as forks, spoons, glasses, or cups. If an individual with mumps uses a utensil and then another person uses the same utensil without proper cleaning, the virus can be transferred from the infected person’s saliva or respiratory secretions to the utensil. If the second person then uses the contaminated utensil and touches their mouth, nose, or eyes, they can become infected with the mumps virus. - Contaminated fomites: Fomites are inanimate objects that can become contaminated with the virus. If a person touches a contaminated surface, such as a doorknob or a tissue, and then touches their mouth, nose, or eyes, they can become infected with the mumps virus.
Contagious period: Affected individuals are contagious approximately 3 days before the onset of symptoms, which can include fever and malaise, and continue to be contagious for up to 9 days after the parotid gland becomes swollen.
🔸Pathophysiology:
1. Nasopharyngeal entry: The mumps virus enters the body through the nasopharynx, which is the upper part of the throat behind the nose. This can occur when an individual inhales respiratory droplets containing the virus, typically from an infected person who coughs or sneezes nearby. The virus establishes its initial infection in the mucous membranes of the nasopharynx.
- Replication in mucous membranes and lymph nodes: Once inside the body, the mumps virus begins to replicate within the mucous membranes of the nasopharynx. The virus attaches to specific receptors present on the surface of the host cells and enters them. Once inside the cells, the virus uses the host’s cellular machinery to produce viral proteins and genetic material, leading to the production of more viral particles.
Simultaneously, the virus also gains access to nearby lymph nodes. Lymph nodes are part of the body’s immune system and play a crucial role in filtering and monitoring the lymphatic fluid. The mumps virus is carried by immune cells called lymphocytes from the initial infection site to the lymph nodes. Within the lymph nodes, the virus continues to replicate, leading to the further production of viral particles.
- Viremia and secondary infection of salivary glands: Following replication in the mucous membranes and lymph nodes, the mumps virus enters the bloodstream, resulting in viremia. Viremia refers to the presence of the virus in the blood. Through the bloodstream, the virus can reach various organs and tissues throughout the body.
One of the primary targets of the mumps virus is the salivary glands, particularly the parotid glands. The parotid glands are the largest of the salivary glands and are located on the sides of the face, in front of the ears. The virus infects the glandular cells within the parotid gland, causing inflammation and swelling. This swelling of the parotid gland is characteristic of mumps and can be visibly observed as swelling around the jawline and cheeks.
- Further dissemination: While the primary site of infection is the parotid gland, the mumps virus can potentially spread to other organs and tissues in the body. This secondary dissemination occurs through the bloodstream and can involve various glands and organs.
- Lacrimal glands: The virus can infect the lacrimal glands, which are responsible for tear production. This can lead to inflammation and swelling of the lacrimal glands, resulting in dry eyes or eye redness in some individuals with mumps.
- Thyroid gland: The thyroid gland, located in the neck, can also be affected by the mumps virus. Infection of the thyroid gland can result in thyroid inflammation (thyroiditis) and may cause symptoms such as neck pain or discomfort.
- Mammary glands: In some cases, the mumps virus can disseminate to the mammary glands, which are responsible for milk production in females. This can lead to breast inflammation (mastitis) in affected individuals.
- Pancreas: The mumps virus can infect the pancreas, an organ located in the abdomen that plays a crucial role in producing insulin and regulating blood sugar levels. Pancreatic infection can cause pancreatitis, an inflammation of the pancreas, which may result in abdominal pain, nausea, and vomiting.
- Testes and Ovaries: Mumps can also affect the reproductive organs. In males, the virus may infect the testes, leading to orchitis (inflammation of the testicles). Orchitis can cause testicular pain, swelling, and, in rare cases, fertility problems. In females, the virus can infect the ovaries, causing oophoritis (inflammation of the ovaries), though this is less commonly observed.
- Central Nervous System (CNS): In rare instances, the mumps virus can cross the blood-brain barrier and infect the central nervous system (CNS). This can lead to a condition known as mumps meningitis or encephalitis, characterized by inflammation of the protective membranes surrounding the brain and spinal cord. CNS involvement can result in symptoms such as headache, neck stiffness, confusion, and even seizures.
🔸Clinical Features:
Incubation period: The time between exposure to the mumps virus and the onset of symptoms is typically around 16-18 days.
▪️Classic Presentation:
♦️Stage 1 or Prodromal stage This refers to the initial phase of mumps infection, lasting for about 3-4 days. During this phase, individuals may experience symptoms such as low-grade fever, malaise, and headache. ♦️Stage 2: The hallmark feature of mumps is inflammation of the salivary glands, particularly the parotid glands, which are located on the sides of the face, in front of the ears. The duration of parotitis is typically at least 2 days, but it can persist for more than 10 days.
Initially, individuals with mumps may present with local tenderness, pain, and earache. Unilateral swelling of the salivary gland, affecting the lateral cheek and jaw area, is commonly observed. As the disease progresses, both salivary glands are usually affected. Redness in the area of the parotid duct and possible protruding ears may also be present. In some cases, a flat, red rash can develop on the face and spread to other parts of the body.
Duration of parotitis: at least 2 days (may persist > 10 days)
Symptoms
May initially present with local tenderness, pain, and earache
Unilateral swelling of the salivary gland (lateral cheek and jaw area); During the course of disease, both salivary glands are usually swollen.
Redness in the area of the parotid duct
Possible protruding ear: The swollen parotid pushes the ipsilateral ear outward and upward.
A flat, red rash that begins on the face and disseminates to the rest of the body can occur.
Chronic courses: Chronic or prolonged courses of mumps are rare.
▪️Subclinical presentation:
In some cases, mumps infection may be subclinical, meaning there are no apparent symptoms. However, even in these cases, individuals can still transmit the virus to others.
It is important to note that about 15-20% of mumps cases can be asymptomatic, meaning individuals may not experience any noticeable symptoms.
🔸Diagnostics
Pathogen detection
Real-time reverse transcriptase PCR (rRT-PCR) on serum or buccal or oral swab
Viral culture (e.g., on CSF, urine, or saliva)
Serology: Positive serum IgM suggests recent infection and confirms the diagnosis.
Relative lymphocytosis
↑ CRP, ↑ ESR
↑ Amylase
🔸Management:
Mumps is usually self-limited with a good prognosis (unless complications arise). Treatment is mainly supportive care.
Medication for pain and fever (e.g., acetaminophen)
Bedrest
Adequate fluid intake
Avoidance of acidic foods and drinks
Ice packs to soothe parotitis
Isolate the patient. [8]
All patients: Isolate for 5 days from the development of parotid swelling.
Hospitalized patients: Initiate droplet precautions.
🔸Complications:
▪️Encephalitis (< 1% of cases)
- Reduced consciousness, seizures
- Neurological deficits: cranial nerve palsy, hemiplegia, sensorineural hearing loss (rare)
▪️Hearing loss (extremely rare)
Classification of Flaviviridae:
Pathogenesis of Yellow Fever:
Yellow fever is called so because it is often associated with jaundice. In severe cases of yellow fever, the virus can cause liver damage, leading to the accumulation of bilirubin in the body. This yellow discoloration gave rise to the name “yellow fever.” It is important to note that not all individuals with yellow fever will develop jaundice, but the name of the disease reflects this common symptom.
🔸Epidemiology:
Yellow fever is endemic in tropical regions of South America and Sub-Saharan Africa.
Asia, Europe, North America, and Australia are free of yellow fever (except for occasional imported cases).
🔸Etiology:
Caused by Yellow fever virus
▪️Transmission:
Yellow fever is primarily transmitted through the bite of infected mosquitoes, specifically the Aedes aegypti species. These mosquitoes become infected with the yellow fever virus when they feed on the blood of an infected person or animal.
- Mosquito acquisition of the virus:
- When an Aedes aegypti mosquito feeds on the blood of an infected person or animal, it takes in the yellow fever virus along with the blood.
- The virus then infects the mosquito’s body, specifically its midgut, where it begins to replicate and multiply.
- Dissemination of the virus within the mosquito:
- As the yellow fever virus continues to replicate, it spreads from the mosquito’s midgut to other organs, including the salivary glands.
- This process typically takes several days.
- Transmission to humans:
- When an infected mosquito bites a human, it injects its saliva into the person’s skin, along with the yellow fever virus if it is infected.
- The virus can then enter the human bloodstream through the mosquito’s saliva, allowing it to spread throughout the body.
- Urban transmission cycle:
- In urban areas where Aedes aegypti mosquitoes are common, the yellow fever virus can be transmitted directly between infected humans and mosquitoes.
- Infected humans serve as a source of the virus for the mosquitoes.
- When an infected mosquito bites another person, it can transmit the virus through its saliva, potentially leading to the spread of yellow fever within the population.
🔸Clinical Features:
Incubation Time:
- The incubation period for yellow fever is typically around 3 to 6 days. This refers to the time between when a person is infected with the virus and when they start experiencing symptoms.
🔸Clinical Features:
- The majority of individuals who are infected with the yellow fever virus do not exhibit any symptoms and remain asymptomatic. However, in symptomatic patients, the disease follows a classic progression in three stages.
▪️ Stage 1 or Period of Infection (3-4 days):
- This stage begins with a sudden onset of high fever, which can reach temperatures as high as 41°C (105°F).
- Headaches and chills are common symptoms during this period.
- Nausea and vomiting may occur, contributing to feelings of general malaise.
▪️ Stage 2 or Period of Remission (up to 2 days):
- After the initial period of infection, there is a temporary easing of symptoms and a decline in fever.
- During this remission period, individuals may experience some relief from their symptoms, and they may feel relatively better.
▪️ Stage 3 or Period of Intoxication (only in approximately 15% of symptomatic patients):
- In some cases, the disease progresses to a more severe stage known as the period of intoxication.
- Hemorrhage, or bleeding, may occur, manifesting as epistaxis (nosebleeds), mucosal bleeding (bleeding from the gums or other mucous membranes), melena (dark, tarry stools), hematuria (blood in the urine), or black vomit.
- Multiorgan dysfunction can occur, leading to conditions such as acute kidney and liver failure.
- Abdominal pain and severe jaundice (yellowing of the skin and eyes) may also be present.
During the Period of Intoxication in yellow fever, approximately 15% of symptomatic patients experience more severe manifestations of the disease. This stage is characterized by two main features: hemorrhage and multiorgan dysfunction.
- Hemorrhage:
- Hemorrhage refers to abnormal bleeding within the body. In yellow fever, it can manifest as various types of bleeding, such as epistaxis (nosebleeds), bleeding from the gums or other mucous membranes (mucosal bleeding), melena (dark, tarry stools), hematuria (blood in the urine), or black vomit.
- The exact mechanism of hemorrhage in yellow fever is not fully understood. However, it is thought to be a result of the virus directly affecting blood vessels, leading to their dysfunction and subsequent bleeding.
- Multiorgan Dysfunction:
- Yellow fever can cause multiorgan dysfunction, particularly affecting the liver and kidneys.
- Liver involvement can result in severe jaundice, where there is a yellowing of the skin and eyes. The virus can directly damage liver cells, leading to liver dysfunction and impaired liver function.
- Kidney involvement can manifest as acute kidney failure, where the kidneys are unable to adequately filter waste products from the blood. This can result in decreased urine output and accumulation of toxins in the body.
The exact mechanisms by which yellow fever leads to multiorgan dysfunction are not fully understood. However, it is believed that the virus directly targets and infects these organs, causing cellular damage and impairing their normal function.
It’s important to note that the Period of Intoxication occurs in a subset of individuals with symptomatic yellow fever, and not all patients progress to this stage. The severity of symptoms and the likelihood of progressing to this stage can vary among individuals.
It’s important to note that not all symptomatic patients progress to the period of intoxication, and the severity of symptoms can vary from person to person. The disease can range from mild cases with flu-like symptoms to severe cases involving organ failure and hemorrhage.
🔸Diagnosis:
▪️Laboratory tests
- ↑ ALT/AST
- Leukopenia
- In period of intoxication: Thrombocytopenia, ↑ PTT
- Signs of organ failure (see acute liver failure, acute renal failure)
▪️Virus detection
- PCR
- ELISA
▪️Liver biopsy
- Used for definitive diagnosis (e.g., postmortem)
- Must not be done while the patient has an active yellow fever infection
- May show Councilman bodies (eosinophilic apoptotic globules). Councilman bodies are apoptosis remnants of hepatocytes.
🔸Management:
- Symptomatic treatment
- No specific antiviral treatment is available
- Avoid NSAIDs that increase the risk of bleeding (e.g., aspirin, ibuprofen, naproxen) in patients with confirmed or suspected yellow fever infection!
Dengue Fever Pathogenesis:
🔸Epidemiology:
Distribution: tropical regions worldwide, particularly Asia (e.g., Thailand)
Incidence
Most common viral disease affecting tourists in tropical regions
🔸Etiology:
- Caused by Dengue virus
▪️Transmission:
Dengue fever is primarily transmitted through the bite of infected mosquitoes, specifically the Aedes aegypti species (These mosquitoes also transmit Yellow Fever virus, Zika virus, and Chikungunya virus). These mosquitoes become infected with the Dengue virus when they feed on the blood of an infected person or animal.
- Mosquito acquisition of the virus:
- When an Aedes aegypti mosquito feeds on the blood of an infected person or animal, it takes in the Dengue virus along with the blood.
- The virus then infects the mosquito’s body, specifically its midgut, where it begins to replicate and multiply.
- Dissemination of the virus within the mosquito:
- As the Dengue virus continues to replicate, it spreads from the mosquito’s midgut to other organs, including the salivary glands.
- This process typically takes several days.
- Transmission to humans:
- When an infected mosquito bites a human, it injects its saliva into the person’s skin, along with the Dengue virus if it is infected.
- The virus can then enter the human bloodstream through the mosquito’s saliva, allowing it to spread throughout the body.
- Urban transmission cycle:
- In urban areas where Aedes aegypti mosquitoes are common, the Dengue virus can be transmitted directly between infected humans and mosquitoes.
- Infected humans serve as a source of the virus for the mosquitoes.
- When an infected mosquito bites another person, it can transmit the virus through its saliva, potentially leading to the spread of yellow fever within the population.
🔸Clinical Features:
Dengue Fever has 3 main clinical entities:
1- Dengue Fever:
The Dengue Fever Classical presentation is the most common and typical presentation. It has 2 subtypes of clinical presentations: Dengue without warning signs and Dengue with warning signs
▪️Dengue without warning signs:
- The incubation period of Dengue Fever is 4-10 days.
- The febrile phase of Dengue Fever is 2-7 days.
🔺 The clinical features of this Subtype includes:
- High fever (40°C) PLUS 2 of the following symptoms during the febrile phase indicate dengue
- Severe headache
- Retro-orbital pain
- Severe arthralgia and myalgia (often referred to as “break-bone fever”)
- Maculopapular, measles-likeexanthem (typically appears 2–5 days after fever onset)
- Generalized lymphadenopathy
- Positive capillary fragility test:
Capillary fragility refers to the susceptibility of small blood vessels called capillaries to rupture or leak. In dengue fever, the dengue virus leads to the activation of the immune system and the release of various substances that affect the integrity of blood vessels.
The capillary fragility test is a simple diagnostic test used to assess the fragility of capillaries. During the test, a blood pressure cuff is placed on the upper arm and inflated to temporarily stop blood flow. After a few minutes, the cuff is released, allowing blood to flow back into the arm. In individuals with normal capillary fragility, no visible signs occur. However, in cases of dengue fever, the capillaries may be more fragile and leaky.
The underlying physiology behind the capillary fragility observed in dengue fever involves the disruption of the endothelial cells that line the capillaries. The dengue virus and the immune response it triggers can cause damage to these cells, leading to increased permeability and fragility of the capillaries. As a result, when blood flow is restored after the cuff is released, the fragile capillaries may rupture or leak, leading to the appearance of small red or purple spots called petechiae on the skin.
Children are usually asymptomatic
▪️Dengue with warning signs:
In dengue fever, the illness progresses through different phases. The critical phase is a period during the course of the disease where there is an increased risk of the patient’s condition worsening. It typically occurs around 3 to 7 days after the onset of symptoms.
During the critical phase, certain changes occur in the body that can lead to more severe symptoms or complications. These changes primarily involve increased vascular permeability, which means that blood vessels become more leaky. This increased permeability can result in the leakage of fluid from blood vessels into tissues, leading to symptoms like plasma leakage, edema, and potentially even organ dysfunction.
Additionally, the critical phase is associated with abnormalities in the clotting mechanisms of the body. This can lead to issues with bleeding and the formation of blood clots in smaller blood vessels.
The timing of the critical phase is often marked by the abatement of fever. As the fever subsides, the risk of clinical deterioration increases. This is why it is important to closely monitor patients during this period for any signs of worsening symptoms or complications.
🔺 Patients at risk of having warning signs during critical phase include:
- Individuals with a history of previous dengue infection
- Infants < 1 year of age
- Patients with severe comorbidities
🔺 Some warning signs that may indicate a worsening condition during the critical phase include:
- Abdominal pain: Severe or persistent abdominal pain can be an indicator of worsening dengue fever.
- Persistent vomiting: Continuous vomiting can lead to dehydration and electrolyte imbalances, which can worsen the overall condition.
- Lethargy or restlessness: Significant changes in energy levels or mental status, such as excessive tiredness or agitation, can suggest worsening symptoms.
- Enlarged liver (> 2 cm): Palpation of an enlarged liver during physical examination can be a sign of liver involvement and potentially severe dengue.
- Signs of fluid accumulation: Pleural effusion (fluid around the lungs) and/or ascites (fluid in the abdominal cavity) can develop during the critical phase, indicating increased vascular permeability and leakage.
- Hemorrhagic manifestations: Petechiae (small red or purple spots on the skin), epistaxis (nosebleeds), and gingival bleeding (bleeding from the gums) are signs of abnormal clotting and increased fragility of blood vessels.
The critical phase is a crucial period where prompt medical intervention is necessary to manage any complications that may arise and prevent further deterioration.
2- Severe Dengue or Dengue Hemorrhagic Fever (DHF):
Severe dengue, also known as dengue hemorrhagic fever (DHF), is a potentially life-threatening form of dengue fever. It occurs as a result of an abnormal immune response in individuals who have been previously infected with one serotype of the dengue virus and are reinfected with a different serotype.
DHF typically occurs as a result of an antibody-dependent reaction in patients who are reinfected with a different serotype
During the initial infection with one serotype of the dengue virus, the immune system produces antibodies to fight off the virus and clear the infection. These antibodies are specific to that particular serotype and can effectively neutralize and eliminate the virus.
However, if a person is later infected with a different serotype of the dengue virus, the antibodies produced during the initial infection may not fully recognize and neutralize the new virus. Instead of effectively eliminating the virus, these antibodies can attach to the new virus particles and form immune complexes.
These immune complexes can then bind to specific immune cells, such as monocytes and macrophages, through receptors on their surface. This binding process is facilitated by the Fc portion of the antibodies in the immune complexes.
The entry of the immune complexes into immune cells can enhance the replication of the virus within these cells. This happens because the immune cells have receptors for the Fc portion of the antibodies, which can facilitate the internalization of the virus into the cell. Once inside the cell, the virus can replicate and cause further damage.
▪️Timing: Severe dengue typically develops around one week after the onset of symptoms, as the initial fever subsides. This distinguishes it from the milder form of dengue fever, in which it occurs after the initial fever subsides.
▪️Incidence: Severe dengue occurs in approximately 1-2% of dengue cases.
▪️Clinical Features of Severe Dengue:
🔺Temperature change: During severe dengue, there may be a temperature change. This can vary from hypothermia, where the body temperature drops below normal, to a second spike in fever.
🔺Hemorrhagic manifestations: One of the key features of severe dengue is thrombocytopenia, which is a decrease in platelet count to less than 100,000/mm3. This can lead to severe hemorrhagic manifestations, such as: - Petechiae - Ecchymoses - Purpura - Hematemesis - Melena (dark, tarry stools)
🔺Severe organ involvement: Severe dengue can affect multiple organs, resulting in significant organ dysfunction.
- Hepatomegaly: During physical examination, an enlarged liver (hepatomegaly) may be observed, indicating liver involvement.
- Liver failure: In severe cases, the liver dysfunction can progress to liver failure, which can have serious consequences.
- Changes in mental status: The dengue virus can affect the central nervous system, leading to changes in mental status such as confusion.
🔺Severely increased vascular permeability: One of the main characteristics of severe dengue is the severe increase in vascular permeability. This means that blood vessels become more leaky, leading to fluid leakage from the blood vessels into surrounding tissues. This can result in various manifestations, such as:
- Pleural effusion: Fluid accumulation around the lungs can cause respiratory distress and difficulty breathing.
- Ascites: Fluid accumulation in the abdominal cavity can lead to abdominal pain and distension.
- Severe changes in hematocrit (Hct): Hematocrit levels, which reflect the proportion of red blood cells in the blood, can be significantly altered in severe dengue. This can result in either an increase (hemoconcentration) or decrease (hemodilution) in hematocrit levels due to fluid shifts.
🔺Positive capillary fragility test
3- Dengue Shock Syndrome (DSS):
Develops due to further deterioration of severe dengue
Presence of both symptoms of severe dengue and circulatory collapse and shock due to plasma leakage
So when Severe dengue + Shock = Dengue Shock Syndrome
🔸Diagnosis:
▪️Laboratory tests
- Leukopenia
- Neutropenia
- Thrombocytopenia
-↑ AST
- Hct significantly increased or decreased in DHF (due to plasma leakage)
▪️Confirmation of diagnosis:
🔺Acute phase (≤ 7 days after symptom onset): - Serologic tests: MAC-ELISA to detect IgM - Molecular Tests (NAAT) to detect viral RNA - NS1 antigen test: detection of the Dengue NS1 antigen (Dengue non-structural protein 1) via ELISA 🔹Allows early detection of the viral antigen in the serum 🔹A positive test confirms the diagnosis (without identifying the dengue serotype) 🔹A negative test does not rule out dengue infection; IgM testing should be performed 🔹Not recommended after day 7 of symptomatic infection (low sensitivity)
- Tissue tests (IHC)🔺Convalescent phase (> 7 days after symptom onset):
- Serologic tests (IgM, IgG)
- Molecular Tests (NAAT)
- Tissue tests (IHC)
🔸Management:
▪️Symptomatic treatment
▪️Fluid administration to avoid dehydration
▪️Acetaminophen
▪️Dengue with warning signs and severe dengue:
- Blood transfusions in case of significant internal bleeding (e.g., epistaxis, gastrointestinal bleeding, or menorrhagia)
- Urgent resuscitation with IV fluids
▪️Avoid NSAIDs that increase the risk of bleeding (e.g., aspirin, ibuprofen, naproxen) in patients with confirmed or suspected Dengue fever infection!
What is an Arbovirus:
A virus that is transmitted by an Arthropod Vector (Ticks, mosquitoes).
An arbovirus is a type of virus that is transmitted to humans or animals through the bites of arthropod vectors, such as mosquitoes, ticks, or sandflies. The term “arbovirus” is derived from “arthropod-borne virus.”
Examples: Dengue virus, Yellow Fever virus, Zika virus
An arthropod vector refers to an organism, typically an insect or arachnid, that can transmit disease-causing microorganisms, such as viruses or bacteria, from one host to another. Arthropods are a large group of invertebrates that includes insects like mosquitoes, ticks, and flies, as well as arachnids like spiders and mites.
In the context of disease transmission, arthropods act as carriers or vectors of these disease-causing microorganisms. They become infected with the pathogen when they feed on the blood of an infected individual or come into contact with an infected source. Once the arthropod is infected, it can then transmit the pathogen to a new host when it feeds or bites again.
Arthropods can transmit diseases through various mechanisms. For example, mosquitoes can transmit diseases like malaria, dengue, and Zika virus when they bite an infected person and then bite another person, injecting the pathogen into their bloodstream. Ticks can transmit Lyme disease and other infections when they bite and remain attached to their host for an extended period.
Pathogenesis of Zika Virus:
🔸Epidemiology:
The Zika virus is mainly found in tropical and subtropical regions. Before 2015, there were only a few reported cases of Zika virus in Africa, southeast Asia, and some Pacific islands.
However, since 2015, there have been epidemic outbreaks of Zika virus in South America, especially in Brazil. During this time, there was a significant increase in the number of people infected with the virus in these areas.
🔸Etiology:
Pathogen: Zika virus
Genus: flavivirus, type of arbovirus
Positive-sense, single-stranded, enveloped RNA
▪️Route of Transmission of Zika Virus:
1. Vector-borne transmission: The most common route of Zika virus transmission is through the bite of infected mosquitoes, primarily the Aedes aegypti mosquito. This mosquito species is known to be a vector for various diseases, including Zika virus, Dengue Virus, Yellow Fever virus, and chikungunya. When a mosquito bites a person who is infected with the Zika virus, it can acquire the virus from the person’s blood. The mosquito can then transmit the virus to another person when it bites them.
2. Transplacental transmission: Another important route of Zika virus transmission is from an infected pregnant woman to her fetus. This is known as transplacental transmission. The virus can cross the placenta and infect the developing fetus, potentially causing a range of birth defects and developmental problems. It is important for pregnant women to take precautions to avoid exposure to the Zika virus, especially in areas where the virus is prevalent.
- Sexual transmission: The Zika virus can also be transmitted through sexual contact. It has been found that the virus can persist in the semen of infected men for an extended period, even months after the initial infection. This means that a man who has been infected with Zika can transmit the virus to his sexual partners, both through vaginal and anal intercourse. It is recommended that individuals practice safe sex or abstain from sexual activity if they have been diagnosed with Zika or have been in an area with active Zika transmission.
Zika virus is the only arbovirus that can also be transmitted sexually.
🔸Clinical Features:
- Incubation Period: 2–14 days
- Approx. 80% of cases remain asymptomatic
- In symptomatic patients, the manifestations are usually mild and last for 2–7 days
- Low-grade fever
- Flu-like symptoms: headache, arthralgia, myalgia, non-purulent conjunctivitis, malaise
- Maculopapular, pruritic rash (20% of cases)
▪️Asymptomatic cases: Approximately 80% of individuals infected with Zika virus do not experience any symptoms. These individuals are considered asymptomatic. Despite not showing any signs of illness, they can still spread the virus to others through mosquito bites or other routes of transmission.
▪️Mild symptoms: In symptomatic patients, the manifestations of Zika virus infection are usually mild. The symptoms typically last for 2 to 7 days. Common symptoms include:
- Low-grade fever: Patients may experience a slight increase in body temperature but not a high fever.
- Flu-like symptoms: Headache, arthralgia (joint pain), myalgia (muscle pain), non-purulent conjunctivitis (redness and irritation of the eyes), and malaise (general feeling of discomfort or unease).
- Maculopapular rash: Around 20% of Zika virus-infected individuals develop a rash, which is characterized by red, raised spots on the skin that are itchy (pruritic). This rash is called maculopapular.
🔸Diagnosis:
▪️Laboratory tests
- Increased Levels of Acute Phase Reactants: Due to acute inflammation there will be increased levels of acute phase reactants.
- Leukopenia: Due to bone marrow suppression and destruction of White blood cells.
- Thrombocytopenia
- Increased LDH (Lactate Dehydrogenase): LDH is an enzyme found in many organs and tissues, including the liver, heart, kidneys, and red blood cells. Elevated LDH levels can indicate cellular damage or inflammation in these organs. In the context of Zika virus infection, increased LDH levels may be a result of tissue damage caused by the virus or an immune response to the infection.
- Increased γ-GT (Gamma-Glutamyl Transferase): γ-GT is an enzyme primarily found in the liver. Elevated γ-GT levels are often associated with liver damage or dysfunction. In the case of Zika virus infection, increased γ-GT levels may indicate liver involvement or inflammation caused by the virus.
▪️Definitive diagnosis
- During the first 7 days of the infection: PCR detects Zika virus RNA in blood and/or urine samples
- During days 7–28: RT-PCR and/or serology
- After 28 days: serology confirms Zika virus antibodies
🔸Management:
▪️Definitive therapy does not yet exist.
▪️Treatment is primarily symptomatic with rest, oral/IV fluids, and/or acetaminophen to relieve fever and pain.
▪️To prevent bleeding, NSAIDs and aspirin should be avoided until dengue has been excluded as a diagnosis.
🔸Complications
▪️Guillain-Barré syndrome (GBS): Zika virus infection has been linked to an increased risk of developing GBS.
▪️Pregnancy related Complications:
🔺Congenital Zika syndrome: When a pregnant woman is infected with Zika virus, the virus can be transmitted to the developing fetus. Congenital Zika syndrome refers to a range of birth defects and developmental abnormalities that can occur in babies exposed to Zika virus during pregnancy. It causes growth restriction and significant CNS complications in neonates resulting from intrauterine transmission of the Zika virus. These can include:
- Microcephaly
- Ventriculomegaly (enlargement of the brain’s fluid-filled spaces)
- Subcortical calcifications (abnormal calcium deposits in the brain)
- Spasticity, hyperreflexia, seizures
- Ocular abnormalities: Zika virus infection can cause ocular abnormalities in newborns, such as pigmentary retinal mottling, which refers to changes in the pigmented layer at the back of the eye.
- Sensorineural hearing loss: Some infants exposed to Zika virus during pregnancy may experience sensorineural hearing loss
🔺Miscarriage: Zika virus infection during pregnancy has also been associated with an increased risk of miscarriage or stillbirth.
What is Congenital Zika syndrome:
🔺Congenital Zika syndrome:
When a pregnant woman is infected with Zika virus, the virus can be transmitted to the developing fetus. Congenital Zika syndrome refers to a range of birth defects and developmental abnormalities that can occur in babies exposed to Zika virus during pregnancy. It causes growth restriction and significant CNS complications in neonates resulting from intrauterine transmission of the Zika virus. These can include:
- Microcephaly
- Ventriculomegaly (enlargement of the brain’s fluid-filled spaces)
- Subcortical calcifications (abnormal calcium deposits in the brain)
- Spasticity, hyperreflexia, seizures
- Ocular abnormalities: Zika virus infection can cause ocular abnormalities in newborns, such as pigmentary retinal mottling, which refers to changes in the pigmented layer at the back of the eye.
- Sensorineural hearing loss: Some infants exposed to Zika virus during pregnancy may experience sensorineural hearing loss.
Pathogenesis of West Nile Fever, Murray Valley encephalitis (MVE), St. Louis encephalitis:
What is the genetic material type, genetic material shape, and capsid shape of Influenza Virus:
Capsid: Helical in shape
Genetic Material: Negative Sense Single Stranded RNA that is Linear and segmented in shape with 8 segments.
The shape of the genome is linear and segmented. There are 8 linear segments that makeup the genome.
What is the genetic material type, genetic material shape, and capsid shape of HIV?
🔸HIV are Enveloped RNA viruses
🔸They have 2 copies of a Positive Sense Single Stranded RNA genome
🔸They are Linear in shape
🔸They have Complex and Conical Capsid shape
