Viral Replication Flashcards

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1
Q

What is the viral life cycle?

A
  • attachment: attachment to host cell receptor proteins
  • entry: entry into cell
  • uncoating
  • expression: transcription + translation
  • replication: viral genome replication
  • assembly
  • egress: budding/egress from host cell
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2
Q

What is the attachment protein & receptor molecule for SARS CoV-2?

A
  • attachment protein: S glycoprotein
  • receptor molecule: angiotensin converting enzyme 2 (ACE@)
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3
Q

What is the attachment protein & receptor molecule for HIV?

A
  • attachment protein: gp120
  • receptor molecule: CD4 plus chemokine co-receptor
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4
Q

What is the attachment protein & receptor molecule for influenza?

A
  • attachment protein: hemagglutinin
  • receptor molecule: sialic acid
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5
Q

What happens during uncoating?

A
  • non-enveloped viruses: partial degradation via acidification
  • enveloped viruses: fusion with cell membrane pulls nucleocaspid apart & releases genome into cytoplasm
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6
Q

How are viral mRNAs synthesized?

A
  • host RNA poly -> DNA viruses
  • viral RNA poly -> minus-sense RNA viruses
  • host ribosomes -> plus sense RNA viruses
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7
Q

Where do RNA viruses replicate?

A

in the cytoplasm

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8
Q

What sense of RNA is used for mRNA & as a template for mRNA?

A
  • plus sense -> mRNA
  • minus sense -> template
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9
Q

Where do DNA viruses replicate?

A

in the nucleus

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10
Q

Where do poxviruses replicate?

A

cytoplasm

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11
Q

What happens during assembly?

A
  • non-enveloped: self assembly of capsomere subunits
  • enveloped: depositionof viral glycoproteins onto host cell membrane
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12
Q

What happens during egress/budding?

A
  • non-enveloped: cause cell lysis to release new viruses
  • enveloped: bud at plasma membrane
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13
Q

What are the attachment inhibitors?

A

passive immunization
1. hyperimmune gamma globulin
* CMV, HAV, HBV, RSV
2. monoclonal abs
* RSV -> anti F
* ZEBOV -> anti GP
* SARS CoV 2 -> anti-S

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14
Q

What are the entry inhibitors?

A

HIV drugs
1. co-receptor antagonists
* maraviroc -> CCR5 inhibitor
* ibalizumab -> anti-gp 120 monoclonal ab
2. fusion inhibitors
* enfuvirtide -> gp41 peptide

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15
Q

What are the uncoating inhibitors?

A

influenza entry drugs
1. adamantanamine derivative
* blocks M2 channel -> prevents uncoating
* rapid development of resistance
* only works for influenza A

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16
Q

What are the expression inhibitors?

A
  1. viral RNA poly inhibitors
    * only works on RNA viruses
    * nucleoside & non-nucleoside inhibitors
  2. influenza endonuclease inhibitors
    * baloxavir marboxil
    * prevents 5’ cap snatching
17
Q

What are the characteristics of Acyclovir (ACV, Zovirax) as a DNA polymerase inhibitor?

A
  • guanosine analog
  • selectivity against HSV-1, HSV-2, VZV
    1. Requires phosphorylation by viral thymidine kinase. (ACV -> ACV-MP)
    2. ACV-TP specifically inhibits viral DNA polymerase by competition with GTP.
    3. Chain termination of nascent DNA by incorporation of ACV-MP.
18
Q

What are the characteristics of guanosine as a DNA polymerase inhibitor?

A
  • guanosine analog
  • selectivity against CMV, HSV
    1. Requires phosphorylation by HSV TK or CMV UL97 gene (CMV does not encode a TK gene).
    2. GCV-TP specifically inhibits viral DNA polymerase by competition with GTP.
    3. Chain termination of nascent DNA by incorporation of GCV-MP.
19
Q

What are the viral resistances to acyclovir or ganciclovir?

A
  1. Mutation of TK gene (HSV)
    * TK-negative mutants
    * TK-low expression
    * TK mutants (cannot phosphorylate ACV, GCV)
  2. Mutations in the viral DNA polymerase -> result in cross-resistance to drugs that act directly on DNA polymerase.
20
Q

What are the characteristics of Foscarnet (phosphonoformic acid) as a viral DNA polymerase inhibitor?

A
  • organic analog of inorganic pyrophosphate
  • acts directly on viral DNA polymerase
21
Q

What are the characteristics of Cidofovir (cytosine; HPMPC) as a viral DNA polymerase inhibitor?

A
  • nucleoside analog with phosphonate group
  • in vitro activity against HSV-1, HSV-2, VZV, CMV, EBV, adenovirus, HPV, human polyoma virus.
22
Q

What are the characteristics of Adefovir (PMEA), tenofovir (PMPA) as a viral DNA polymerase inhibitor?

A
  • Acyclic nucleoside phosphonate
  • Activity against retroviruses and HBV.
23
Q

What are the characteristics of nucleoside analogs as a reverse transcriptase inhibitor?

A
  • Require phosphorylation
  • Act as chain terminators of nascent viral DNA
24
Q

What are the characteristics of non-nucleoside inhibitors as a reverse transcriptase inhibitor?

A
  • Specifically bind non-substrate binding pocket of HIV reverse transcriptase
  • Inhibit enzymatic activity
25
Q

What are assembly inhibitors?

A
  • Protease Inhibitors
  • Prevents cleavage of viral proteins by viral protease
  • HCV, SARS CoV-2 -> blocks cleavage intracellularly
  • HIV -> blocks cleavage after particle release
26
Q

What are budding/egress inhibitors?

A
  • influenza egress inhibitors
  • oseltamivir & zanamivir -> Inhibits neuraminidase to prevent proper release from the host cell
27
Q

What are cellular proteins?

A
  • IMP Dehydrogenase inhibitors (Ribavirin)
  • Inhibits the formation of GTP, which is critical to viral genome formation