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M1 FMK > Virology > Flashcards

Virology Flashcards

1
Q

Proteinaceous capsids

A

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

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2
Q

Icosahedral capsids

A

All naked virsues have iscosahedral capsids, some enveloped virsues do as well

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3
Q

Helical capsids

A

Only found in enveloped viruses

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4
Q

What is an exception to the rule that: “enveloped viruses are not stable in the environment”

A

Poxviruses

Generally, enveloped viruses are sensitive to inactivation by low pH, heat, drying, dtergents, lipid solvents an

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5
Q

What type of capsid do naked viruses have?

A

Icosahedral capsids

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6
Q

What viral genomes are the same polarity as eukaryotic mRNA?

A

Positive polarity ss genomes

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7
Q

What viral genomes are complimentary to eurkaryotic mRNA?

A

Negative polarity ss genomes

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8
Q

What viral genomes can be directly translated by host cell ribosomes?

A

single-stranded positive polarity RNA viruses

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9
Q

Most fecal/oral transmitted viruses are _____ ?

A

Naked viruses

Only few enveloped virsues are fecal/oral transmitted

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10
Q
A
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11
Q

What naked virus is sensitive to low pH - cannot pass through GI tract?

A

Rhinoviruses

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12
Q

What enveloped virus can pass through GI tract and be transmitted through the fecal/oral route?

A

Coronaviruses

Pox??

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13
Q

Retroviridae

A

diploid (+) ssRNA

Naked virus

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14
Q

Parvoviridae

A

ssDNA

Naked virus

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15
Q

Papovaviridae

A

dsDNA

Naked virus

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16
Q

Adenoviridae

A

dsDNA

Naked virus

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17
Q

Herpesviridae

A

dsDNA

Enveloped virus

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18
Q

Poxviridae

A

dsDNA

Enveloped virus

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19
Q

Hepadnaviridae

A

partially double-stranded DNA - circular

Enveloped virus

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20
Q

Pciornaviridae

A

(+) ssRNA

Naked virus

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21
Q

Caliciviridae

A

(+) ssRNA

Naked virus

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22
Q

Togaviridae

A

(+) ssRNA

Enveloped virus

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23
Q

Flaviviridae

A

(+) ssRNA

Enveloped virus

i.e. Zika virus

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24
Q

Coronaviridae

A

(+) ssRNA

Enveloped virus

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25
Q

Bunyaviridae

A

segmented (-) ssRNA

Enveloped virus

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26
Q

Arenaviridae

A

segmented (-) ssRNA

Enveloped virus

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27
Q

Orthomyxoviridae

A

Segmented (-) ssRNA

Enveloped virus

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28
Q

Paramyxoviridae

A

(-) ssRNA

Enveloped virus

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29
Q

Rhabdoviridae

A

(-) ssRNA

Enveloped virus

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30
Q

Filoviridae

A

(-) ssRNA

Enveloped virus

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31
Q

Reoviridae

A

Segmented dsRNA

Naked virus

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32
Q

Productive viral infection

A

Infection of a host cell that produces infectious progeny virions

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33
Q

Cell/tissue tropism

Virology

A

The cell or tissue type(s) in which a virus productively replicates

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34
Q

DNA dependent DNA polymerase

A

Enzyme that copies DNA from a DNA template (DNA replication)

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35
Q

DNA dependent RNA polymerase

A

Enzyme that copies RNA from a DNA template (transcription)

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36
Q

RNA dependent RNA polymerase

A

Enzyme that copies RNA from and RNA template (RNA replication)

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37
Q

RNA dependent DNA polymerase

A

aka reverse transcriptase

Enzyme that copies DNA from an RNA template

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38
Q

What polymerases would a virus need to code for in its own genome?

Not supplied by host cell

A

RNA dependent RNA polymerase

RNA dependent DNA polymerase

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39
Q

List the steps of the viral replication cycle

A
  1. Attachment/adsoprtion
  2. Entry/penetration
  3. Uncoating
  4. Synthesis of viral macromolecules
  5. Assembly/maturation
  6. Release
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40
Q

VAP and receptor for SARS-CoV-2

A

Viral attachment protein (VAP) - The viral spike (S) protein

Receptor - ACE2 enzyme (normally regulates BP by cleaving angiotensin II into angiotensin)

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41
Q

Mechanism of cell entry: enveloped vs. naked virsuses

A

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

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42
Q

Most DNA viruses replicated their genome in the nucleus, except for?

A

Poxviruses - replicate in the cytoplasm

Codes for their own DNA dependent DNA polymerase, other DNA replication factors, and DNA dependent RNA polymerase

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43
Q

Most RNA viruses replicate in the cytoplasm, except for?

A

Orthomyxoviruses and retroviruses - replicate in the nucleus

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44
Q

Replication of a typical (+) ssRNA virus

A

i.e. hep C and SARS-CoV-2

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45
Q

Replication of a typical (-) ssRNA virus

A

i.e. respiratory syncytial virus and influenza virus

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46
Q

HIV replication (example of retrovirus replication)

A
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47
Q

HIV VAP and receptor

A

VAP - gp120 glycoprotein

Receptor - CD4 protein

Two host co-receptors: CCR-5 and CXCR-4

Viral fusion protein gp41

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48
Q

Immune cells that kill virus-infected cells

A

NK cells and CD8+ cytotoxic T cells

49
Q

How do virus particles assemble after translation in a host cell?

A

They spontaneously assemble

Enveloped virsues assemble underneath a region of host membrane where viral envelope proteins have been inserted

50
Q

What makes prions resistant to many different proteases?

A

Their beta-pleated structure

51
Q

How do prions make copies of themselves?

A

Templated mediated protein refolding

52
Q
A

C. No plaques/No plaques/Plaques

53
Q
A

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)

54
Q

Most (+) ssRNA viruses replicate in the host cytoplasm. What (+) ssRNA virus replicates its genome in the host nucleus?

A

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

55
Q

Which infectious agent uses reverse transcriptase (RT), integrase (INT), and protease (PRO) enzymes during its replication?

A

HIV (retroviruses)

56
Q

Which type of viral genome is most likely to be translated immediately upon entry into the host cell cytoplasm to produce a viral polyprotein?

A

(+) ssRNA viruses

57
Q

Viruses with highest mutation rate

A

Viruses with RNA genome that use their own RNA polymerase (does not have proofreading capability)

58
Q

Host range/tissue tropism alteration

Viruses

A

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

59
Q

Antigenic drift

A

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

60
Q

Reassortment

A

Only occurs in viruses w/ segmented genomes

Influenza A - antigenic shift

61
Q

Recombination

A

Only occurs w/ viruses that have unsegmented DNA gemones

62
Q

Antigenic shift

A

Rapid (one generation) change in antigenic composition of a virus

Due to a stable genome change (not a mutation)

Result of genome reassortment

63
Q

What causes a viral epidemic?

What type of evolutionary shift?

A

Antigenic drift

64
Q

What causes viral pandemics?

What type of evolutionary shift?

A

Antigenic shift

65
Q

How differentiate complentation/pseudotype formation from antigenic shift/drift?

A

Complementation and pseudotype formation only last one generation

66
Q

Complementation

A
67
Q

Phenotypic masking

Pseudotype formation

A

Occur when two viruses swap envelope or capsid proteins (genomes are packaged in each other’s capsids/evelopes)

68
Q

Where do viral drug resistance mutations occur in viral genes?

A
  1. The drug target
  2. Another enzyme required for drug activation
69
Q

Acyclovir

A

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

70
Q

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?

A

Envelope glycoprotein, not capsid protein

71
Q

Which is NOT a possible outcome of mutations in a viral genome?

A

Antigenic shift

72
Q
A

Reassortment

Only occurs in viruses with segmented genome

73
Q
A

Complementation

74
Q

Viral target and enzyme required to activate acyclovir

A

Target: DNA-dependent DNA polymerase

Enzyme: thymidine kinase

75
Q

Antigenic shift

A

Occurs when viruses w/ segmented genomes that are derived from different host species swap genome segments

76
Q

Most common origin of viral mutation

A

RNA viruses:

RNA-dependent RNA pol and RNA-dependent DNA pol do not have proofreading cabaility

77
Q

Drugs targets for influenza

A

Cap-dependent exonuclease

Neuraminidase

78
Q
A

D. Acyclovir

79
Q

Non-HIV antiviral that inhibits viral entry and penetration

A

Docosanol (Abreva) - OTC topical

80
Q

Antiviral used to Tx influenza A and B that inhibits viral replication

A

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

81
Q

Acyclovir

Spectrum

A

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

82
Q

Valacyclovir

A

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)

83
Q

Ribavirin

A

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

84
Q

Which of the following drugs prevents viral penetration into host cells as its antiviral MOA?

A. Acyclovir
B. Ritonavir
C. Foscarnet
D. Docossanol

A

D. Docosanol (Abreva)

85
Q

What antiviral is used for acyclovir-resistant herpes?

A

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)

86
Q

Nueraminidase inhibitors

A

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

87
Q

Paxlovid

A

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

88
Q

Remdesivir

A

IV medication that inhibits SARS-CoV-2 RNA-dependent RNA polymerase

89
Q

Key proteins involved in Hep C replication

A

NS3/4A - protease

NS5A - Replication complex (RNA rep)

NS5B - RNA polymerase

NS = nonstructural protein

90
Q

Hep C Tx against genotypes 1, 4, 5, and 6

A

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)

91
Q

Hep C Tx against all six major HCV genotypes

A

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)

92
Q

Glecprevir

A

NS3/4A inhibitor (protease inhibitor)

Used in Hep C Tx

93
Q

Hep C drug regimen drug interactions

A

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

94
Q

Ledipasvir

A

NS5A inhibitor (RNA replication complex)

Used in Hep C Tx

95
Q

Veltpatasvir

A

NS5A inhibitor (RNA replication complex)

Hep C Tx

96
Q

Sofosbuvir

A

NS5B inhibitor (RNA polymerase inhibitor)

Hep C Tx

97
Q

Interferons

A

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

98
Q

Monoclonal AB’s to prevent RSV

A

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

99
Q

Zidovudine (AZT), Emtricitabine, and Tenofovir

A

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

100
Q

Efavirenz

A

Non-nucleoside reverse transcriptase inhitior

Metabolized by P450s

HIV Tx

Adverse effects:

CNS effects (abnormal dreams, sedation)
Severe rashes - including SJS

101
Q

Lopinavir and Ritonavir

A

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

102
Q

Enfuvirtide

A

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

103
Q

Maraviroc

A

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

104
Q

Raltegravir

A

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

105
Q

Lenacapavir

A

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

106
Q

Clinical approach to Tx and prophylactic HIV therapy

A
107
Q
A

A. Oseltamivir (Tamiflu)

108
Q
A

C. Nucleoside reverse transcriptase inhibitors

109
Q
A

D. Ritonavir

110
Q

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

A

B. Ribavirin

111
Q

What is the MOA of sofosbuvir?

A

Interferes w/ Hep C viral RNA replication

NS5B inhibitor (RNA polymerase inhibitor)

Hep C Tx

112
Q

Ritonavir is often added to other antiviral therapies. What is the primary reason for this?

A

It is a potent P450 inhibitor (increases duration of other drugs)

113
Q
A

C. Valgnaciclovir

114
Q
A

D. Pegylation

115
Q
A

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

116
Q
A

A. A NRTI - cause pancreatitis

117
Q
A

D. Efavirenz (allosteric inhivitor of reverse transcriptase)

118
Q

What HIV drugs cause sxs that parallel diabetes?

A

Protease inhibitors like Lopinavir

119
Q

Enfuvirtide

A

HIV drug that blocks fusion of virus (enfuvirtide)

M1 FMK (55 decks)

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