Virology Flashcards
Proteinaceous capsids
All viruses contain proteinaceous capsids - protects the genome from damge and participates in attachment and entry of host cells (said to be a vehicle for transfer of nucleic acid from one cell to another)
3 types:
1. Icosahedral
2. Helical
3. Complex
Icosahedral capsids
All naked virsues have iscosahedral capsids, some enveloped virsues do as well
Helical capsids
Only found in enveloped viruses
What is an exception to the rule that: “enveloped viruses are not stable in the environment”
Poxviruses
Generally, enveloped viruses are sensitive to inactivation by low pH, heat, drying, dtergents, lipid solvents an
What type of capsid do naked viruses have?
Icosahedral capsids
What viral genomes are the same polarity as eukaryotic mRNA?
Positive polarity ss genomes
What viral genomes are complimentary to eurkaryotic mRNA?
Negative polarity ss genomes
What viral genomes can be directly translated by host cell ribosomes?
single-stranded positive polarity RNA viruses
Most fecal/oral transmitted viruses are _____ ?
Naked viruses
Only few enveloped virsues are fecal/oral transmitted
What naked virus is sensitive to low pH - cannot pass through GI tract?
Rhinoviruses
What enveloped virus can pass through GI tract and be transmitted through the fecal/oral route?
Coronaviruses
Pox??
Retroviridae
diploid (+) ssRNA
Naked virus
Parvoviridae
ssDNA
Naked virus
Papovaviridae
dsDNA
Naked virus
Adenoviridae
dsDNA
Naked virus
Herpesviridae
dsDNA
Enveloped virus
Poxviridae
dsDNA
Enveloped virus
Hepadnaviridae
partially double-stranded DNA - circular
Enveloped virus
Pciornaviridae
(+) ssRNA
Naked virus
Caliciviridae
(+) ssRNA
Naked virus
Togaviridae
(+) ssRNA
Enveloped virus
Flaviviridae
(+) ssRNA
Enveloped virus
i.e. Zika virus
Coronaviridae
(+) ssRNA
Enveloped virus
Bunyaviridae
segmented (-) ssRNA
Enveloped virus
Arenaviridae
segmented (-) ssRNA
Enveloped virus
Orthomyxoviridae
Segmented (-) ssRNA
Enveloped virus
Paramyxoviridae
(-) ssRNA
Enveloped virus
Rhabdoviridae
(-) ssRNA
Enveloped virus
Filoviridae
(-) ssRNA
Enveloped virus
Reoviridae
Segmented dsRNA
Naked virus
Productive viral infection
Infection of a host cell that produces infectious progeny virions
Cell/tissue tropism
Virology
The cell or tissue type(s) in which a virus productively replicates
DNA dependent DNA polymerase
Enzyme that copies DNA from a DNA template (DNA replication)
DNA dependent RNA polymerase
Enzyme that copies RNA from a DNA template (transcription)
RNA dependent RNA polymerase
Enzyme that copies RNA from and RNA template (RNA replication)
RNA dependent DNA polymerase
aka reverse transcriptase
Enzyme that copies DNA from an RNA template
What polymerases would a virus need to code for in its own genome?
Not supplied by host cell
RNA dependent RNA polymerase
RNA dependent DNA polymerase
List the steps of the viral replication cycle
- Attachment/adsoprtion
- Entry/penetration
- Uncoating
- Synthesis of viral macromolecules
- Assembly/maturation
- Release
VAP and receptor for SARS-CoV-2
Viral attachment protein (VAP) - The viral spike (S) protein
Receptor - ACE2 enzyme (normally regulates BP by cleaving angiotensin II into angiotensin)
Mechanism of cell entry: enveloped vs. naked virsuses
Enveloped virus - enter by fusion of viral enveloped with a cellular membrane (mediated by viral fusion protein - part of VAP complex) - binding of VAP complex to receptor causes endocytosis (either conformational change of VAP complex occurs spontaneously or following a pH drop of the endosome)
Naked virus - typically enter cell through receptor-mediated endocytosis
Most DNA viruses replicated their genome in the nucleus, except for?
Poxviruses - replicate in the cytoplasm
Codes for their own DNA dependent DNA polymerase, other DNA replication factors, and DNA dependent RNA polymerase
Most RNA viruses replicate in the cytoplasm, except for?
Orthomyxoviruses and retroviruses - replicate in the nucleus
Replication of a typical (+) ssRNA virus
i.e. hep C and SARS-CoV-2
Replication of a typical (-) ssRNA virus
i.e. respiratory syncytial virus and influenza virus
HIV replication (example of retrovirus replication)
HIV VAP and receptor
VAP - gp120 glycoprotein
Receptor - CD4 protein
Two host co-receptors: CCR-5 and CXCR-4
Viral fusion protein gp41
Immune cells that kill virus-infected cells
NK cells and CD8+ cytotoxic T cells
How do virus particles assemble after translation in a host cell?
They spontaneously assemble
Enveloped virsues assemble underneath a region of host membrane where viral envelope proteins have been inserted
What makes prions resistant to many different proteases?
Their beta-pleated structure
How do prions make copies of themselves?
Templated mediated protein refolding
C. No plaques/No plaques/Plaques
D. The viral genome is transported to the host cell nucleus and is used as a template to produce the provirus DNA
(+) ssRNA genome that contains enzyme that uses RNA as a template to produce complementary DNA (reverse transcriptase) ID’s this virus as a retrovirus
In retroviral replication the (+) ssRNA viral genome is not tranlated in the cytoplasm to produce a polyportein, as are the genome of all other (+) ssRNA viruses. Instead, the retroviral genome is tranport to the nucleus, where it is used as a template by the virion-associated reverse transcriptase enzyme to produce a dsDNA copy of the viral genome (proviral DNA)
Most (+) ssRNA viruses replicate in the host cytoplasm. What (+) ssRNA virus replicates its genome in the host nucleus?
HIV and all other retroviruses
The (+) ssRNA genome is transported into the host nucleus where the virion-associated reverse transcriptase uses it as a template to make dsDNA copy of the genome (proviral DNA). Proviral DNA is then integrated into the host cell genome by the viral integrase enzyme.
Progeny viral genome are made by host RNA poylmerase II
Which infectious agent uses reverse transcriptase (RT), integrase (INT), and protease (PRO) enzymes during its replication?
HIV (retroviruses)
Which type of viral genome is most likely to be translated immediately upon entry into the host cell cytoplasm to produce a viral polyprotein?
(+) ssRNA viruses
Viruses with highest mutation rate
Viruses with RNA genome that use their own RNA polymerase (does not have proofreading capability)
Host range/tissue tropism alteration
Viruses
Mutations usually occur in the VAP gene - allows for virus to either use a new host cell receptor use the same receptor in a different host species
Antigenic drift
Over time, there is an accumulation of mutations in a viral gene that causes gradual changes in protective epitopes within the viral proteins
Reason for repeated vaccinations for influenza and SARS-CoV-2
Reassortment
Only occurs in viruses w/ segmented genomes
Influenza A - antigenic shift
Recombination
Only occurs w/ viruses that have unsegmented DNA gemones
Antigenic shift
Rapid (one generation) change in antigenic composition of a virus
Due to a stable genome change (not a mutation)
Result of genome reassortment
What causes a viral epidemic?
What type of evolutionary shift?
Antigenic drift
What causes viral pandemics?
What type of evolutionary shift?
Antigenic shift
How differentiate complentation/pseudotype formation from antigenic shift/drift?
Complementation and pseudotype formation only last one generation
Complementation
Phenotypic masking
Pseudotype formation
Occur when two viruses swap envelope or capsid proteins (genomes are packaged in each other’s capsids/evelopes)
Where do viral drug resistance mutations occur in viral genes?
- The drug target
- Another enzyme required for drug activation
Acyclovir
Activated when it is phosphorylated by the herpes simplex virus (HSV) thymidine kinase enzyme - once activated it acts as an antagonsit of the viral DNA polymerase
Resistance mutations can occur in the drug target gene (HSV DNA polymerase) or in the HSV thymidine kinase gene
SARS-CoV-2 is an enveloped virus with a (+) ss RNA genome. This virus has undergone genome mutations that changed its host range from bats to humans. In which viral gene would those mutations MOST LIKELY be found?
Envelope glycoprotein, not capsid protein
Which is NOT a possible outcome of mutations in a viral genome?
Antigenic shift
Reassortment
Only occurs in viruses with segmented genome
Complementation
Viral target and enzyme required to activate acyclovir
Target: DNA-dependent DNA polymerase
Enzyme: thymidine kinase
Antigenic shift
Occurs when viruses w/ segmented genomes that are derived from different host species swap genome segments
Most common origin of viral mutation
RNA viruses:
RNA-dependent RNA pol and RNA-dependent DNA pol do not have proofreading cabaility
Drugs targets for influenza
Cap-dependent exonuclease
Neuraminidase
D. Acyclovir
Non-HIV antiviral that inhibits viral entry and penetration
Docosanol (Abreva) - OTC topical
Antiviral used to Tx influenza A and B that inhibits viral replication
Boloxavir
Inhibits endonuclease activity of the polymerase acidic protein (aka cap-dependent endonuclease) - influenza-speicific enzyme in the viral RNA polymerase complex
Should not be taken w/ cations
Decreases efficacy of flu vax w/i 48 hrs and after 2 wks
Used for drug resistant flu
Acyclovir
Spectrum
Guanosine analog and Tx’s Herpes and Varicella zoster
Excreted renally - can cause glomerulonephritis and precipitate in the urine
High IV doses can have CNS effects (i.e lethargy, tremor, confusion, hallucination, seizures, and coma)
Must first be phosphorylated by thymidine kinase
Valacyclovir
Prodgrug that is converted to acyclovir by liver and intestinal enzymes - has greater bioavailability than acyclovir and require less frequent dosing
Other prodrugs with similar MOA: penciclovir and famciclovir (famciclovir is prodrug of penciclovir)
Ribavirin
Another guanosine analog that becomes phosphorylated by host enzymes that inhibit viral RNA polymerase
Administered via inhalation to Tx RSV and IV to Tx Lassa fever or Hantavirus
Very mutagenic, carcinogenic, teratogenic
Which of the following drugs prevents viral penetration into host cells as its antiviral MOA?
A. Acyclovir
B. Ritonavir
C. Foscarnet
D. Docossanol
D. Docosanol (Abreva)
What antiviral is used for acyclovir-resistant herpes?
Foscarnet - inhibits viral DNA polymerase w/o needing activation
Also used to Tx CMV retinitis infections
Administered IV and penentrates well into tissues (including CNS)
Nueraminidase inhibitors
Oseltamivir (oral) and Zanamivir (inhaled)
Neuraminidase helps release new viruses from infected cells by cleaving sialic acid residues from surface proteins of infected cells
Impede viral spread by altering viral particle release and aggregation
Zanamivir can cause bronchospasm
Paxlovid
Nirmaterlvir-ritonavir
Nirmatrevlir is main antiviral component working as a protease inhibitor (to stop replication)
Ritonavir - boosts level of main antiviral by inhibiting its metabolism (through inhibition of CYP450 enzymes)
Not recommended for Pt’s with severe kidney disease (eGFR < 30 mL/min) or severe liver disease
Remdesivir
IV medication that inhibits SARS-CoV-2 RNA-dependent RNA polymerase
Key proteins involved in Hep C replication
NS3/4A - protease
NS5A - Replication complex (RNA rep)
NS5B - RNA polymerase
NS = nonstructural protein
Hep C Tx against genotypes 1, 4, 5, and 6
At least two different drugs are used simultaneously (that target different steps in viral replication) to prevent drug resistant
Harvoni - Sofusbuvir (NS5B inhibitor) + Ledipasvir (NS5A inhibitor)
Hep C Tx against all six major HCV genotypes
At least two different drugs are used simultaneously (that target different steps in viral replication) to prevent drug resistant
Sofosbuvir (NS5B inhibitor) + Velpatasvir (NS5A inhibitor)
Glecprevir
NS3/4A inhibitor (protease inhibitor)
Used in Hep C Tx
Hep C drug regimen drug interactions
Ledipasvir (NS5A inhibitor) requires acid for aborption - ppi’s inhibit and should be avoided
Serious bradycardia when sofosbuvir is used w/ amiodarone
Many hep C drugs interact w/ statins (risk of myopathy)
Many Hep C Tx’s are metabolized by or influenced by liver enzymes such as CYP450 enzymes as well as transport proteins like p-glycoprotein and OATP
Ledipasvir
NS5A inhibitor (RNA replication complex)
Used in Hep C Tx
Veltpatasvir
NS5A inhibitor (RNA replication complex)
Hep C Tx
Sofosbuvir
NS5B inhibitor (RNA polymerase inhibitor)
Hep C Tx
Interferons
Have antiviral, anticancer, and immune-regulating effects
Work by enhancing the activity of immune cells like macrophages and lymphocytes
Side effects: early Tx Pts may experience flu-like sxs. W/ longer Tx’s side-effects like nerve damage and bone marrow suppression can occur
Commonly used alongside other Hep C Tx’s
Some interferons are pegylated (polyethylene glycol chain attached) to exten half-life - can be dosed once a wk
Monoclonal AB’s to prevent RSV
Palizumab and Nirsevimab
Target RSV F protein (fusion protein on surface of virus) and prevent virus from fusing and entering
Used to prevent RSV in high-risk individuals
Zidovudine (AZT), Emtricitabine, and Tenofovir
AZT and emtricitabine are nucleoside reverse transcriptase inhibitors
Tenofovir is the only nucleotide RTI
These drugs are phosphorylated by the host then blocks the reverse transcriptase enzyme and cause chain termination
HIV Tx
Adverse effects:
Bone marrow suppression
Pancreatitis
Peripheral neuropathy
Myopathy
Lactic acidosis - rare
Efavirenz
Non-nucleoside reverse transcriptase inhitior
Metabolized by P450s
HIV Tx
Adverse effects:
CNS effects (abnormal dreams, sedation)
Severe rashes - including SJS
Lopinavir and Ritonavir
Protease inhibitors
Ritonavir is a low potency protease inhibitor but incredibly potent P450 inhibitor - often combined to boost concentrations of other drugs metabolized by CYP450 enzymes
Prevent maturation of viral particles
HIV Tx
Adverse effects:
Increased trigs and LDL
Insulin resistance
Risk of bleeding in hemophiliacs
Enfuvirtide
HIV fusion inhibitor
36 AA peptide that binds to the gp-41 protein on HIV - prevents from fusing w/ and infecting host cells (administered by injection)
HIV Tx
Adverse effects:
Bacterial pneumonia
Hypersensitivity rx’ns
Injection site rx’ns
Maraviroc
Binds to CCR5 co-receptor blocking HIV entry
Only effective early in therapy - late HIV viruses do not express co-receptor (late viruses use CXCR4 co-receptors)
HIV Tx
Adverse effects:
Liver damage that mimics allergic rx’n
Cardiovascular events
Increased risk of infections
Raltegravir
Inhibits the integrase enzyme, which integrates HIV viral DNA into the DNA of CD4 lymphocytes
No cross-resistance w/ other HIV meds
HIV Tx
Adverse effects:
GI upset
Elevated creatin kinase
Muscle pain
Immun reconstitution syndrome
Lenacapavir
Capsid inhibitor that interferes w/ multiple stages of the viral life cycle - i.e. nuclear transport, assembly, and release
Used in heavily Tx-experienced Pt’s w/ multi-drug-resistant HIV-1
Administered twice a year and may remain in circulation for over a year
Substrate for P-glycoprotein, UGT1A1, and CYP3A
Clinical approach to Tx and prophylactic HIV therapy
A. Oseltamivir (Tamiflu)
C. Nucleoside reverse transcriptase inhibitors
D. Ritonavir
Which antiviral drug is teratogenic and should not be administered in an aerosolized form by pregnant healthcare workers when it is prescribed to Tx chisdren w/ RSV?
A. Acyclovir
B. Ribavirin
C. Ritonavir
D. Zidovudine
B. Ribavirin
What is the MOA of sofosbuvir?
Interferes w/ Hep C viral RNA replication
NS5B inhibitor (RNA polymerase inhibitor)
Hep C Tx
Ritonavir is often added to other antiviral therapies. What is the primary reason for this?
It is a potent P450 inhibitor (increases duration of other drugs)
C. Valgnaciclovir
D. Pegylation
C. Zidovudine
Nucleoside reverse transcriptase inhibitor
RItonavir - potent P450 inhibitor and weakest of the protease inhibitor
Lopinavir - stronger protease inhibitor
Maraviroc - CCR5 antagonist
Raltegravir - integrase inhibitor
A. A NRTI - cause pancreatitis
D. Efavirenz (allosteric inhivitor of reverse transcriptase)
What HIV drugs cause sxs that parallel diabetes?
Protease inhibitors like Lopinavir
Enfuvirtide
HIV drug that blocks fusion of virus (enfuvirtide)
