Virus Structure and Function Flashcards
Antigen Detection
- Direct test on PT specimen
- Detecting specific antigens of the particular organism you’re looking for
- Similar to pregnancy test
Attachment - Direct Fusion
The virus directly fuses with the host plasma membrane and the nucleic acid is then released.
Some viruses, particularly ENVELOPED VIRUSES (HIV, influenza) can fuse their lipid envelope directly with the host cell membrane.
Attachment - Endocytosis
Internalized into a vacuole in the host cell, transported to an endosome and then the nucleic acid is released.
Attachment - Nucleic Acid Translocation
- A rare feature of non-enveloped viruses, though it can occur in enveloped viruses
- Caspid adheres to the host cell membrane
- Partial rearrangement of the virion
- Nucleic acid passes directly into the host cell
Attachment - Receptor-Mediated Entry + 2 Examples
- Specific receptors are used by the virus to gain entry into the cell
- Engagement of the receptors will often lead to changes in the structure of the virus that further help with entry.
Examples include
1. HIV
- HIV uses the CD4 receptor with CCR5 or CXCR4 as co-receptors required for viral entry into host cells
- 10% of people of European descent have a deletion mutation in CCR5 (CCR5-Delta32). Heterozygotes may experience slower rates of progression if infected, and homozygotes are highly resistant to infection.
- Thought to be linked to the Bubonic plague
- SARS-CoV2
- Uses the ACE2 receptor to mediate entry.
- Expressed in the nostrils, GI tract, and neurons/glial cells
- Infection of cells expressing ACE2 in the olfactory epithelium can lead to inflammation which may reduce the sense of smell
Bacteria vs Viruses
Viruses are significantly smaller
Bacteria self-replicate by binary fission, viruses do not
Bacteria have cellular machinery including ribosomes, viruses do not
Can a Virus Be Both Lysogenic and Lytic? Example?
Yes.
- Oral herpes (HSV1)
- There is an acute period of pain and inflammation (lytic), it then disappears and is clinically silent (lysogenic)
- Chicken Pox (Verisella Zoster)
- Same thing, acute period followed by remission
Often brought on by stress, trauma, or other infections
Classifying Viruses
- +/-
- Sense Strand (Positive Sense RNA)
• Definition:
• The + sense strand is equivalent to the coding strand of DNA or RNA.
• It is in the correct orientation to be directly translated into proteins by the host cell’s ribosomes.
• In Viral Genomes:
• Positive-sense RNA viruses (e.g., coronaviruses, polio virus) have genomes that act directly as mRNA. These can be immediately used for protein synthesis after entry into the host cell.
• Example: The viral RNA of SARS-CoV-2 is + sense RNA, which can be directly read by ribosomes.
- Sense Strand (Positive Sense RNA)
- Antisense Strand (Negative Sense RNA)
• Definition:
• The - sense strand is complementary to the sense strand and cannot be directly translated into proteins.
• It must first be converted into a complementary + sense strand (via RNA-dependent RNA polymerase) before translation can occur.
• In Viral Genomes:
• Negative-sense RNA viruses (e.g., influenza, rabies) carry genomes that must be transcribed into + sense RNA before they can produce proteins.
• These viruses must carry their own RNA-dependent RNA polymerase to perform this conversion inside the host cell.
- Antisense Strand (Negative Sense RNA)
- Sense in Relation to DNA
In the broader sense (pun intended!), the classifications can be related to the sense and antisense strands of DNA:
• Sense Strand (Coding Strand):
• The DNA strand that has the same sequence as the RNA transcript (except for thymine/uracil substitution).
• Equivalent to the + sense strand in RNA.
• Antisense Strand (Template Strand):
• The DNA strand complementary to the RNA transcript and used as the template for RNA synthesis.
• Equivalent to the - sense strand in RNA.
Classifying Viruses
- Structure (3)
- Nucleic acid
- DNA/RNA, single stranded, or double stranded
- How the virus replicates
DNA vs RNA Viruses
- Compare
DNA - Highly Stable
RNA - Highly unstable
RNA viruses mutate MUCH faster than DNA viruses.
If it’s RNA, the chances that there could be resistance are much higher. If it’s DNA, it is more likely to be receptive to treatment. This rule applies across the board.
dsDNA Virus Replication
- Viral DNA is transcribed into viral mRNA by the VIRAL polymerase
- mRNA is translated by HOST ribosomes to make proteins and enzymes that allow for new virus particle production
- It then uses the HOST RNA polymerase to make RNA for capsid proteins and DNA polymerase
- The newly created DNA polymerase can then replicate the viral DNA
Electron Microscopy
Used more in the past when viruses difficult to grow
Impractical and not very sensitive
Tells you the FAMILY but not the actual virus
Exception to the Envelope Rule
POX VIRUSES
- Very stable due to its thick caspid protein. Recent monkeypox outbreaks in hospitals have occurred among workers handling bedding due to its longterm stability outside of the body.
Four Types of Attachment
- Direct Fusion
- Endocytosis (may or may not be receptor mediated)
- Receptor Mediated Entry (HIV, Hep viruses)
- Nucleic Acid Translocation
Latent Infection
- Difficulty in treatment + Example
Eg. HIV
“Introduces itself” into the genetic material. Even if it can’t be detected in blood, it is ‘hiding out’ in stem cells.
Difficulty in treatment arises as it requires getting all of the cells that have integrated pro-viral DNA to be identified and destroyed so as not to act as a source.
Otherwise, as soon as you remove the therapy, it regenerates
Latent Viral Infection
- Definition
- Two examples
- Persistence of viral genomes, but not infectious virions, in host cells without the destruction of the host cell
Examples
1. Herpes Simplex Virus and Varicella-Zoster Virus
- Established latency in sensory neurons
- HIV-1
- Can avoid host immune responses and antiretroviral drugs through latent infection of resting memory CD4(+) T helper cells
Lysogenic Viral Lifecycle
- Clinical relevance
- Steps of Cycle (6)
- Virus enters, infects cell, then ‘hangs out’ for a bit.
- Clinically, they are not apparent. Silent virus. They still replicate but tend to stay ‘under the radar’. No inflammation, no sores etc.
- Viral DNA enters the cell (or RNA is converted to DNA by reverse transcriptase in the case of retroviruses like HIV).
- Certain cellular factors dictate whether the virus enters the lytic cycle (active replication) or lysogenic cycle (latency).
- For bacteriophages, phage DNA integrates into the bacterial chromosome, becoming a prophage.
- The bacterium reproduces, copying the prophage and transmitting it to daughter cells.
- Over time, cell divisions produce a population of bacteria carrying the dormant prophage.
- Occasionally, environmental factors (e.g., stress) trigger the prophage to exit the bacterial chromosome, initiating the lytic cycle.
Lytic Viral Life Cycle
- Clinical Features
- Steps (5)
- Results in the cell ‘blowing up’ at the end.
- Lytic lifecycle viruses are usually clinically quite apparent as they result in the cells themselves being destroyed leading to inflammation etc.
- Bacteriophage attaches to bacterium’s cell wall
- Bacteriophage injects DNA into bacterium
- Bacteriophage takes over bacterium’s metabolism, causing synthesis of new bacteriophage proteins and nucleic acid
- Bacteriophage proteins and nucleic acids assemble into complete bacteriophage particles
- Bacteriophage enzyme lyses the bacterium’s cell wall, releasing new bacteriophage particles that can attack other cells.
Negative Sense (-) RNA Viruses Replication
- The antisense strand. Complementary to the coding sequence that is used by the ribosome to code for proteins
- Has to be converted to the sense (positive) stranded genome prior to mRNA (via Rdrp) and protein production
- The virion-associated RNA polymerase (acting as an Rdrp) results in the positive sense RNA that can then be transcribed to proteins by the host ribosome
PCR
Indeed
Positive Sense (+) RNA Virus Replication + Example
- The sense (coding) strand, used as the template for host ribosomes
- RNA can be directly converted to mRNA (cap/tail etc) and used to make proteins
- No intermediary steps
Example:
SARS-CoV-2 and other coronaviruses (head cold)
Retroviral Replication
- RNA viruses but instead of RNA –> Protein
they go RNA —> DNA —> mRNA —> Protein - Reverse transcriptase enzyme creates a SINGLE strand of viral DNA complementary to the retroviral RNA
- ssDNA is then copied to form complementary DNA
- dsDNA now enters the host cell nucleus, and a later infection develops
RNA Viral Replication
Some act directly as mRNA and can be read by the HOST ribosome
Some are more complex and require extra replicative enzymes to be brought with them
HIGH RATES OF MUTATION DUE TO THE NATURE OF REPLICATION
- Less stable transcript
- Lack the proofreading mechanisms that most host cells have
RNA vs DNA Viruses
- Examples
COVID - RNA virus
Herpes - DNA Virus
DNA viruses tend to be the ones whose disease state persists throughout life (eg herpes, HSV2)
Another example of DNA viruses includes Verisella Zoster (chicken pox). First clinical infection is chicken pox, every subsequent infection is referred to as shingles and is a reactivation of the inocculum that you already had
Serologic Response
- Procedure
- When it’s used
- Detection of the immune response by the host against the infectious agent
- Detecting a specific antibody response (HOST antibody response)
- Commonly used to detect viruses that have a very narrow window of viremia (WNV, Zika) and those that are not culturable (Hep B)
- Can also be used when the virus is at low levels (soon after infection)
Strategies for Detecting Viral Infection (4)
- Direct Detection with Electron Microscopy
- Serology (observe the host’s response to the virus.)
- ELISA
- Lateral flow assay
- IgM (acute infection) IgG antibodies (past infection) - Antigen Testing
- Specific viral proteins (eg nucleocapsid protein in SARS-CoV-2)
- Not as sensitive as PCR - PCR/qPCR
- Most commonly used
- Most sensitive to acute infection
The Caspid
The outermost portion of non-enveloped viruses
- A protein shell enclosing the nucleic acid which provides symmetry and structure to the virus
- Consists of an assembly of identical protein subunits
Three Types of Caspids
- Icosahedral
- Helical
- Spherical
Viral Life Cycle
- Two Types
- Lytic
- Lysogenic
Viral Replication Cycle
- Four Steps
- Attachment
- Entry and Uncoating
- Replication and Assembly
- Egress or Release of the Virus
Virus Classification and Naming System
Classification System Includes
- Nature of nucleic acid (DNA or RNA)
- Symmetry of the caspid (helical, icosahedral)
- Presence of absence of an envelope (enveloped or naked)
- Structure, Size, and Morphology of virus
- Tissue or organ tropism (Adenovirus, Enterovirus, Rhinovirus)
Virus Culture
- Procedure
- Disadvantages
Procedure:
- Growth in tissue culture
Disadvantages:
- Not all viruses can be cultured
- Slow (days to weeks)
- Requires specific cell lines and many different tissue types must be inoculated
Virus Culture
- Cytopathic Effect
- Effects that the virus infection has on the appearance of cells in culture.
- viewed by light microscopy after a PT specimen is inoculated onto the cell culture and the virus has had a chance to replicate
FAIRLY NONSPECIFIC
Virus Structure
- Outer portion
SOME VIRUSES have an outer envelope made up of glycoproteins drawn by the host cell.
Non-enveloped viruses tend to be much more stable than enveloped viruses, and can live on surfaces for up to a week. Eg Norovirus
Within the virus, nucleic acids are enclosed by a Caspid protein shell
Viruses
- Components
- Function of Virion
Components:
- Made up of proteins and ONE type of nucleic acid (DNA or RNA)
- In contrast to bacteria, there has not been a virus discovered that contains both DNA and RNA
Function of Virion (Single virus molecule)
- To deliver its DNA or RNA into a host cell so it can be expressed (transcribed and translated) by a host cell.
- Can infect animal cells, bacteria (bacteriophages), and human cells
Viruses
- Definition
- Obligate parasites that require a host and do not live independently, in contrast to bacteria which live independently of the human body
- Viruses must have ‘something’ that helps them carry out the requirements of life (producing proteins, replication etc)
What is one way that latent infection can occur?
- Triggers
- Example
INTEGRATION OF VIRAL DNA
- For certain viruses, viral DNA can also become integrated with host DNA, leading to latent infection.
- Virus may start to replicate at later times.
Triggers include
- Stress
- UV light
- Hormones
- immune suppression
- several UNKNOWN triggers
Why Are Viruses Called “Obligate Parasites”?
- Viruses have their own enzymes that they carry. In order for a virus to be packaged and infectious, it needs to carry the ‘bare bones’. It WILL carry a viral polymerase. (DNA viruses will often contain a viral DNA polymerase, while RNA viruses will contain Rdrp)
” 1. Viruses have their own enzymes, including polymerases, to perform tasks the host cell cannot. These enzymes are essential for viral replication and packaging.
• DNA viruses may encode a DNA polymerase, while RNA viruses encode RNA-dependent RNA polymerase (RdRP).
• Larger DNA viruses (e.g., herpesviruses) and most RNA viruses carry these polymerases in the virion, but small DNA viruses (e.g., parvoviruses) rely entirely on host machinery.
2. After transcription to RNA:
• DNA viruses use the host RNA polymerase (e.g., RNA Pol II) to transcribe their genomes into mRNA.
• RNA viruses rely on their own RdRP to transcribe RNA genomes.
• All viruses depend on host ribosomes, ATP, and other cellular factors to synthesize proteins and complete their replication cycles.”
- After it gets to RNA, it requires a host polymerase to complete the process along with host ribosomes, ATP and other factors
