Lecture 4 Flashcards
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Mumps, measles, and rubella
Mumps is a viral infection that causes fever, headache, muscle aches, loss of appetite, and swollen salivary glands. It can also cause complications such as meningitis, encephalitis, and infertility.
Measles is a viral infection that causes fever, cough, runny nose, red eyes, and a rash. It can also cause complications such as pneumonia, encephalitis, and death.
Rubella is a viral infection that causes fever, rash, swollen glands, and joint pain. It is usually mild in children, but it can cause serious birth defects if a pregnant woman contracts the virus.
(this is review)
section title
Envelope type
pleomorphic envelope
Capsid type
Helical nucleocapsid
Genome type
Linear
What type of proteins does it carry
nucelocapsid-associated proteins
How can you tell the genera apart?
Through the attachment proteins
Paramyxoviruses can cause what diseases?
Measles and mumps
How do Paramyxoviruses invade cells?
Through membrane fusion and then budding
Mumps attachment proteins
HN: Hemagglutinin-neuraminidase
which is responsible for virus attachment, interacts with the fusion protein in a virus type-specific manner to induce efficient membrane fusion.
Measles viral-attachment proteins
H: Hemagglutinin
It is responsible for binding the virus to the cell that is being infected.
Genera of Paramyxoviruses
Morbillivirus
Paramyxovirus
Pneumovirus
Morbillivirrs
Causes measles
Paramyxovirus
Mumps virus
Paraninfluenza
Pnuemovirus
RSV (respiratory syncytial virus)
Metapneumovirs
Paramyxoviruses Replication Scheme
Same as the other ssRNA (-) Schemes.
Make one positive and use it for viral proteins
Make one positive and then use it to make more negative strands that are used in packaging of the new viruses
NP (Nucleoprotein):
Function: Binds & protects viral RNA..
P (Polymerase Phosphoprotein):
function: Facilitates RNA replication.
L (RNA Polymerase):
Involved in RNA replication.
F Protein (Membrane Protein):
Promotes fusion & viral entry.
HN (Hemagglutinin-Neuraminidase):
Binds surface receptors and has neuraminidase activity.
H (Hemagglutinin):
Binds surface receptors.
M Protein (Matrix Protein):
Involved in the assembly of virions.
Enveloped or not? Togaviruses (rubella)
Enveloped
Capsid type Togaviruses (rubella)
Icosahedral Capsid
genome type. Togaviruses (rubella)
ssRNA (+) Capsid
Glycoprotein spikes
Togaviruses (rubella)
E1 & E2:
E1 Protein Function:
: The E1 protein in rubella virus is involved in the fusion of the viral envelope with the host cell membrane during the process of viral entry. This fusion allows the virus to enter the host cell.
E2 Protein:
The E2 protein in rubella virus is primarily responsible for the attachment of the virus to specific receptors on the surface of host cells. It binds to cellular receptors, facilitating the initial binding of the virus to the host cell.
Where do togaviruses replicate?
IN the cytoplasm
Where do togaviruses infect
Infects the upper respiratory tract
How are they spread
Through viremia to lymphoid tissue, skin and other organs
Main disease togaviruses cause
Rubella
Rubella replications cheme
ssRNA (+)
Same as always
One translated to protein and one translated to negative and then used to make more positive strands
Rubella virus structure
Check slide 11
Capsid Protein
Enveloped etc
Life cycle of Rubella Virus
The life cycle of rubella virus, like many other viruses, involves a series of steps that allow the virus to infect host cells, replicate, and spread. Here is an overview of the rubella virus life cycle:
-
Attachment and Entry:
- The initial step in the rubella virus life cycle is the attachment of the virus to specific receptors on the surface of host cells. In the case of rubella virus, the E2 protein plays a crucial role in this attachment.
- Once attached to the host cell, the virus is internalized into the host cell through endocytosis, a process where the host cell membrane engulfs the virus particle.
-
Uncoating:
- After internalization, the viral envelope fuses with the host cell membrane, releasing the viral genome (single-stranded RNA) into the cytoplasm of the host cell.
-
Translation and Replication:
- The released viral RNA is then translated to produce viral proteins, including replication and structural proteins.
- Viral RNA serves as a template for the replication of new viral RNA strands.
-
Assembly:
- New viral particles are assembled within the host cell. The structural proteins, including the E1 and E2 glycoproteins, are involved in forming the viral envelope.
- The viral genome is encapsulated by the newly formed viral particles.
-
Budding and Release:
- The newly assembled rubella virus particles are transported to the cell surface.
- The virus particles are released from the host cell by budding, a process where the viral envelope is acquired from the host cell membrane, and the mature virus particles are released into the extracellular environment.
-
Infection of New Cells:
- The released rubella virus particles can then infect neighboring host cells, repeating the cycle.
Mumps
Virus Type: Mumps Virus (Paramyxovirus)
Transmission Type: Respiratory droplets, close contact
Incubation Period: 12-25 days
Symptoms: Swelling of salivary glands (parotitis), fever, headache, muscle pain
Duration of Illness: 7-10 days
Rash: No typical rash
Severity: Generally mild, but complications can occur
Fetal Infection: Rare, but possible
Vaccine: Mumps component in MMR (Measles, Mumps, Rubella) vaccine
Measles
Virus Type: Measles Virus (Paramyxovirus)
Transmission Type: Airborne, highly contagious
Incubation Period: 7-14 days
Symptoms: High fever, cough, runny nose, red eyes, characteristic rash
Duration of Illness: About 7-10 days
Rash: Characteristic red, raised rash
Severity: Can be severe with complications, including pneumonia
Fetal Infection: Risk to pregnant women, especially in the first trimester
Vaccine: Measles component in MMR (Measles, Mumps, Rubella) vaccine
Rubella (German Measles)
Virus Type: Rubella Virus (Togavirus)
Transmission Type: Respiratory droplets, close contact
Incubation Period: 12-23 days
Symptoms: Mild rash, fever, swollen lymph nodes
Duration of Illness: About 3 days
Rash: Characteristic pink rash
Severity: Typically mild in children and adults, but can have complications, more severe in pregnant women
Fetal Infection: High risk of congenital rubella syndrome if a pregnant woman is infected
Vaccine: Rubella component in MMR (Measles, Mumps, Rubella) vaccine
Mumps Virus
Highly contagious lytic infection
How does mumps spread in the body?
Viremia
Where is the secondary infection for mumps?
Can spread to the parotid gland
Causes swelling in the neck
(google picture to remember)
Spread of Mumps in the body
Enters in the respiratory tract, replication, viremia, systemic infection, then to the parotid gland, the testes/ovaries/ eye/ear (etc) , the CNS, and the pancreas
Can lead to diabetes or swelling
Measles Virus
Highly contagious
Primary infection of measles
In the epithelial cells
Secondary infection
In lymphocytes and monocytes
How is measles spread through the body?
The lymphatic system
Characteristic symptom of measles
RASH!!!!
Happens because T cells will target the skin blood vessels and endothelial cells
Spread of Measles in the body
Inoculates the respiratory tract, replication, lymphatic spread, viremia, wide dessemination through the whole body, virus infected endothelium, RASH!!!, and then diff. outcomes
Picornaviruses
Picornaviruses are a family of small, non-enveloped RNA viruses that are responsible for a variety of diseases in humans and animals. They are known for their simple, single-stranded RNA genomes and their ability to cause a wide range of illnesses. Here are some key points about picornaviruses:
Enteroviruses
Enteroviruses are a group of viruses that belong to the Picornaviridae family. They are named “enteroviruses” because they typically enter the body through the gastrointestinal tract.
Types of Picornaviruses
Poliovirus - Poliomyelitis (polio)
Coxsackievirus - Hand, foot, and mouth disease, herpangina, myocarditis, viral meningitis
Echovirus - Aseptic meningitis, respiratory illnesses, febrile illnesses
Rhinovirus - Common cold
Enterovirus - Various respiratory and gastrointestinal infections, as well as more serious conditions
Hepatitis A Virus - Hepatitis A
Cardiovirus - Encephalomyocarditis virus (primarily infects rodents)
Enterovirsues
Poliovirus
Coxsackie A virus
Coxsackie B virus
Echovirus
Enterovirus
Rhinovirus
Common cold
Under the umbrella of picornaviruses
Cardiovirus
Encephalomyocarditis virus (EMCV).
Apthovirus
Aphthoviruses belong to the family Picornaviridae and are responsible for causing foot-and-mouth disease (FMD) in cloven-hoofed animals, such as cattle, pigs, sheep, and goats.
Hepatovirus
Hepatitis A
Under the picornaviruses umbrella
Poliovirus time course
4-35 days
Coxsackievirus time course
2-10 days
Echovirus
2-14 days
Meningitis
Entervirus
6-12 days
Causes rash, and febrile illness
Do enteroviruses have an envelope?
No envelope
Capsid shape of enteroviruses
Icosahedral capsid
Genome type: enteroviruses
Small ssRNA (+) viruses
What’s special about enteroviruses genome?
it is linear mRNA genome.
One of the unique features of enteroviruses is that their genome resembles messenger RNA (mRNA), and this characteristic allows for the efficient translation of viral proteins.
Where are enteroviruses replicated & assembled?
The cytoplasm
How resistant to diseases are enteroviruses?
Very resistant!
Enteroviruses can tolerate alot of pH range & this is why they’re GI tract viruses
how are enterviruses transmitted?
Fecal-oral route
Lytic/Non-lyitc?
enteroviruses
Lytic viruses w/ specific tissue tropism
Enteroviruses: Life cycle
Attachment and Entry:
Enteroviruses initially attach to specific receptors on the surface of host cells. Poliovirus, for example, attaches to the poliovirus receptor (CD155) on host cells.
After attachment, the virus enters the host cell through endocytosis.
Uncoating:
Once inside the host cell, the viral capsid is disassembled, and the viral RNA genome is released into the cytoplasm.
Translation and Replication:
The enterovirus genome, which resembles mRNA, is directly translated by host cell ribosomes to produce a single polyprotein.
This polyprotein is then cleaved into individual viral proteins by viral proteases.
Replication of the viral RNA occurs, leading to the synthesis of more viral RNA.
Assembly:
New viral particles are assembled in the cytoplasm, and the viral RNA is encapsidated by structural proteins.
Budding and Release:
The newly formed virus particles are released from the host cell through a process that does not typically involve lysis but rather the extrusion of virus particles.
Infection of New Cells:
The released enterovirus particles can infect neighboring host cells and repeat the replication cycle.
Primary viremia of enteroviruses?
Blood
Secondary viremia of enteroviruses
Target tissues and organs
- includes skin, muscle, brain, meninges, liver
Diseases of enterviruses
Common Cold
Hand, Foot, and Mouth Disease (HFMD)
Aseptic Meningitis
Myocarditis
Pericarditis
Acute Hemorrhagic Conjunctivitis (AHC)
How are enteroviruses transmitted?
through human fecal matter, sewage, solid waste, landfills, etc.
Can survive harsh environments
Cause fever and rash
Herpes Viruses
Herpesviruses are a family of DNA viruses known for their ability to establish latent infections and cause a wide range of diseases in humans and animals. There are eight known human herpesviruses, and each is associated with specific clinical conditions
Do herpres viruses have an envelope?
Yes very much so
Viral-glycorprotien rich envelope
Capsid Type: Herpes
Icosadeltahedral capsid
Virus type? Herpes
dsDNA virus
Genome type: Herpes
Linear genome
What’s used to classify herpesvirus
Site of latent infection & gene structure
Where are herepes replicated and assembled?
In the nucleus
How common are herpes infections?
Pretty common
can be asymptotic and benign for the avg person but theymight be serious in immunocompromised individuals
Morbidity of herepes ?
Can be morbid in the eye, brain or in disseminated infections
Do herepes have specific tropism?
Yes some can have highly specific tropism
How are they released from the host cell? Herpes
Through lysis, exocytosis & cell-cell bridges
There are 3 subfamilies of Herpes viruses. What are they?
Alpha
Beta
Gamma
Alpha Herpesvirus
HERPES SIMPLEX HSV1
HERPES SIMPLEX 2 HSV2
VARICELLA-ZOSTER VIRUS HHV 3
Beta
Cytomegalovirus -HHV
Human Herpesvirus 6 & HHV7
Gamma
Epstien-bar virus EBV : HHV5
Kaposis’s sarcoma-related virus HHV 8
Herpes Replication scheme
dsDNA virus
Converts to MRNA which is then translated to viral proteins
dsDNA is copied and then used in new viruses
Herpes Time Course
(refer to the chart)
Herpes Viruses Structure
(kinda looks like the Bengali flag)
HerpesViruses: Life Cycle
The virus enters the host cell, delivering its double-stranded linear DNA genome.
Circularization of the Genome:
Once inside the host cell, the viral DNA circulates with “sticky ends,” which means the ends of the linear DNA strands can base-pair with each other.
This circularization process transforms the linear DNA into a circular chromosome that can serve as a template for replication and transcription.
Gene Expression and Transcription
The circularized viral DNA contains genes that encode various viral proteins and enzymes.
Early genes are transcribed first, leading to the synthesis of specific viral proteins.
One of these early gene products is the viral DNA polymerase, which is an enzyme responsible for replicating the viral genome.
Concatemeric DNA Formation:
During the replication process, the viral DNA polymerase synthesizes new DNA strands.
Instead of producing individual genome-length DNA molecules, the DNA polymerase creates a long chain of repeated viral genomes, known as a “concatemeric DNA.”
The concatemeric DNA can be very long, containing 20 to 30 or more genome-length copies in a single strand.
Herpes Simplex Virus 1 (HSV-1):
Diseases: Oral herpes (cold sores), herpes labialis, herpetic gingivostomatitis, and can cause genital herpes.
Herpes Simplex Virus 2 (HSV-2):
Diseases: Genital herpes and can also cause oral herpes.
HHV3:
Varicella-Zoster Virus (VZV):
Diseases: Chickenpox (varicella) and shingles (herpes zoster).
Epstein-Barr Virus (EBV):
Infectious mononucleosis (mono), Burkitt’s lymphoma, nasopharyngeal carcinoma, and other lymphoproliferative disorders.
Cytomegalovirus (CMV):
Cytomegalovirus infection, which can be asymptomatic or cause symptoms, particularly in immunocompromised individuals.
Human Herpesvirus 6 (HHV-6):
Roseola infantum (exanthema subitum), a childhood illness with high fever and a characteristic rash.
Human Herpesvirus 7 (HHV-7):
Causes roseola, but its role in disease is less well-understood compared to HHV-6.
Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) or Human Herpesvirus 8 (HHV-8):
: Kaposi’s sarcoma, primary effusion lymphoma, multicentric Castleman disease, and other conditions primarily seen in immunosuppressed individuals, especially those with HIV/AIDS.
HSV-1 & HSV-2
HSV-1 and HSV-2 genomes encode approximately 80 proteins.
These viruses belong to the Alphaherpesvirinae subfamily.
Viral Replication:
Both HSV-1 and HSV-2 follow a similar pattern of viral replication within host cells.
Viral DNA Polymerase:
These herpesviruses encode a viral DNA polymerase, which is crucial for replicating their DNA genomes.
Scavenging Enzymes:
HSV-1 and HSV-2 produce scavenging enzymes that create deoxyribonucleotides, essential building blocks for DNA replication.
Attachment Glycoproteins:
These viruses possess attachment glycoproteins that facilitate their entry into host cells.
Immune Escape Proteins:
HSV-1 and HSV-2 have immune escape proteins that help them evade the host’s immune system.
Lytic Phase: HSV 1 /2
HSV-1 & HSV-2 infect fibroblasts and epithelial cells during the lytic phase.
Latent phase: HSV1/2
During latency, herpesviruses persist in non-dividing cells, primarily neurons.
In non-permissive cells, early and late genes are not expressed.
Latency-Associated Transcripts (LATs):
LATs are non-coding RNAs produced during latency, aiding in immune evasion.
Micro-RNAs:
Micro-RNAs produced during latency inhibit gene expression
Sensory Neurons:
Herpesviruses persist in sensory neurons, such as trigeminal neurons.
This latency helps the virus avoid the host’s immune response, often causing no symptoms.
Immune Evasion:
Herpesviruses block the Transporter Associated with Antigen Processing (TAP).
They express Fc and complement receptors.
This helps the virus evade immune detection.
Reactivation:
Reactivation from latency can occur due to systemic infection, fever, stress, or sun exposure.
It leads to recurrent symptoms or outbreaks.
HSV 1 INFECTION & LATENCY:
HSV infects the host and will establish LATENCY in the trigeminal ganglia.
This is how the virus will remain in the body time and time again
During latency, the virus remains dormant within nerve cells.
Periodically, the virus can reactivate, leading to the appearance of a cold sore on the lips or around the mouth.
Clinical Manifestations of HSV 1
Cold sores, fever blisters, Pharyngitis, Encephalitis
HSV 2
Genital Herpes
neonatal HSV- can be fatal to babies when immunity is not developed
VZV (Varicella-Zoster Virus) - HHV-3
Primary Infection - Chickenpox:
Targets epithelial cells, fibroblasts, and T cells.
‘
Characterized by a widespread rash, fever, and itching.
HHV3:
Virus family
Virus Family: Alphaherpesvirinae subfamily
Recurrent Infection -
Will become Herpes Zoster (Shingles):
Occurs in neurons, particularly the dorsal root or cranial nerve ganglia.
Primary Route of Transmission: HHV3
Contracted through inhalation of respiratory droplets containing the virus.
Where does HHV 3 replicate?
VZV undergoes replication in mucosal epithelial cells during the primary infection. This replication leads to the formation of new virus particles.
How is HHV3 Spread in the body?
Viermia:
VZV can spread systemically via viremia, a condition in which the virus enters the bloodstream. As the virus circulates in the bloodstream, it can reach the skin, leading to the development of characteristic skin lesions. These skin lesions are often described as “pox” and are a hallmark of chickenpox, the primary infection caused by VZV.
VZV virus mechanism
Droplets: Infection often begins with the inhalation of respiratory droplets containing the virus.
Respiratory Tract: The virus initially infects the respiratory tract.
Lymphatics: It can enter the lymphatic system, allowing it to travel through the body.
Liver/Spleen: In some cases, the virus may reach the liver and spleen.
Viremia: The virus can spread systemically through viremia, entering the bloodstream.
Membranes and Skin:
As it circulates in the bloodstream, the virus can reach mucous membranes and the skin, leading to the characteristic skin lesions seen in certain infections.
Latent in Neurons: After the primary infection, the virus establishes latency in neurons, where it remains dormant for an extended period.
EBV (Epstein-Barr Virus) - HHV-4
virus Subfamily: Gammaherpesvirinae
Primary Infection of EBV
During primary infection, EBV replicates actively, leading to lytic infection.
Binds to CR2 receptor expressed on selected epithelial cells and B cells.
Early & Late genes are transcribed & translated
Latent Infection in Memory B Cells:
Following the primary infection, EBV establishes latent infection in memory B cells.
During latency, there’s no active viral replication (no early or late gene expression).
Recurrence can occur when the B cell is activated, leading to virus reactivation.
Immortalization of B Cells:
EBV has the ability to immortalize B cells, preventing their natural cell death.
This contributes to the development of B cell lymphomas, such as African Burkitt lymphoma.
or Nasopharyngeal carcinomas
Forcing the B cells to continue replicating
Infectious mononucleosis (“kissing disease”)
Typically transmitted through the shedding of the virus, often through the exchange of saliva, giving it the nickname “kissing disease.”
Proliferation of B/T cells: EBV
EBV infection leads to the proliferation and activation of B cells, resulting in a massive activation of T cells.
T-Cell-Mediated Immunity
EBV
T-cell-mediated immunity plays a critical role in controlling the EBV infection but also contributes to the symptoms of infectious mononucleosis.
Symptoms of EBV
Lymphocytosis: Characterized by an increase in mononuclear cells in the blood.
Swelling of lymphatic tissue, especially the lymph nodes.
Malaise and a general feeling of unwellness are common symptoms.
EBV Mechanism
EBV in saliva -> B cells/epithelial cells of oropharynx -> B cell proliferation -> activates T cells and can lead to latency or malaise.
B cells in the oropharynx can cause shedding in saliva and pharyngitis
Clinical Syndrome of ESV
Symptoms:
Fatigue
Severe sore throat
High fever
Swollen lymph nodes
Enlarged spleen (potential danger)
Swollen liver
Headaches
Rash (less common)
Muscle aches
Loss of appetite
CMV (Cytomegalovirus) - HHV-5:
Member of the betaherpesvirinae subfamily
Permissive cells that allow HHV5 to replicate
Permissive cells: Fibroblasts, epithelial cells, granulocytes, macrophages.
Latent infection (non-permissive cells)
monocytes, lymphocytes, bone marrow stromal cells
Slow replication favors latent infections
Reactivation in immunocompromised individuals of HHV 5
Can be reactivated in immunocompromised individuals, leading to active infection.
Asymptomatic shedding of HHv5
Asymptomatic Shedding:
Virus can be shed in various body fluids without causing symptoms.
Body fluids include saliva, tears, urine, breast milk, and semen.
CMV: normal infection
Can cause an asymptomatic carrier or mono
CMV: in a neonate
Cytomegalic inclusion disease
CMV in an immunocompromised individual
Multisite symptomatic disease
HHV6
(Roseola, Herpes Lymphotrophic Virus):
Prevalence: HHV6
Nearly everyone is seropositive (has antibodies) to HHV-6 by adulthood.
Replication: HHV6
Replicates in the salivary glands.
Clinical Presentation: HHV6
Typically presents with high fever followed by a rash on the neck and trunk.
Latent Infection HHV6
Virus establishes latent infection in lymphocytes, particularly CD4+ T cells and monocytes.
Productive Infection: HHV6
Reactivates and produces active infection upon T cell activation.
HHV6 REACTION MECHANISM
HHV 6 -> incubation -> fever -> no fever & rash appears -> recovery
HHV-8 (Kaposi Sarcoma-related virus):
Classification:
Similar to EBV (Epstein-Barr virus), belongs to the gammaherpesvirinae subfamily.
Clinical Association:
Associated with rare B cell lymphoma.
Causes opportunistic infections, especially in AIDS patients.
HHV-8 Proteins:
Produces specific proteins with notable functions:
IL-6 homologue
Bcl-2 analog
IL-6 homologue function
Promotes cell growth.
Bcl-2 analog
Prevents programmed cell death (apoptosis).
