Viral Replication Flashcards
What is the viral life cycle?
- 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
What is the attachment protein & receptor molecule for SARS CoV-2?
- attachment protein: S glycoprotein
- receptor molecule: angiotensin converting enzyme 2 (ACE@)
What is the attachment protein & receptor molecule for HIV?
- attachment protein: gp120
- receptor molecule: CD4 plus chemokine co-receptor
What is the attachment protein & receptor molecule for influenza?
- attachment protein: hemagglutinin
- receptor molecule: sialic acid
What happens during uncoating?
- non-enveloped viruses: partial degradation via acidification
- enveloped viruses: fusion with cell membrane pulls nucleocaspid apart & releases genome into cytoplasm
How are viral mRNAs synthesized?
- host RNA poly -> DNA viruses
- viral RNA poly -> minus-sense RNA viruses
- host ribosomes -> plus sense RNA viruses
Where do RNA viruses replicate?
in the cytoplasm
What sense of RNA is used for mRNA & as a template for mRNA?
- plus sense -> mRNA
- minus sense -> template
Where do DNA viruses replicate?
in the nucleus
Where do poxviruses replicate?
cytoplasm
What happens during assembly?
- non-enveloped: self assembly of capsomere subunits
- enveloped: depositionof viral glycoproteins onto host cell membrane
What happens during egress/budding?
- non-enveloped: cause cell lysis to release new viruses
- enveloped: bud at plasma membrane
What are the attachment inhibitors?
passive immunization
1. hyperimmune gamma globulin
* CMV, HAV, HBV, RSV
2. monoclonal abs
* RSV -> anti F
* ZEBOV -> anti GP
* SARS CoV 2 -> anti-S
What are the entry inhibitors?
HIV drugs
1. co-receptor antagonists
* maraviroc -> CCR5 inhibitor
* ibalizumab -> anti-gp 120 monoclonal ab
2. fusion inhibitors
* enfuvirtide -> gp41 peptide
What are the uncoating inhibitors?
influenza entry drugs
1. adamantanamine derivative
* blocks M2 channel -> prevents uncoating
* rapid development of resistance
* only works for influenza A
What are the expression inhibitors?
- viral RNA poly inhibitors
* only works on RNA viruses
* nucleoside & non-nucleoside inhibitors - influenza endonuclease inhibitors
* baloxavir marboxil
* prevents 5’ cap snatching
What are the characteristics of Acyclovir (ACV, Zovirax) as a DNA polymerase inhibitor?
- 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.
What are the characteristics of guanosine as a DNA polymerase inhibitor?
- 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.
What are the viral resistances to acyclovir or ganciclovir?
- Mutation of TK gene (HSV)
* TK-negative mutants
* TK-low expression
* TK mutants (cannot phosphorylate ACV, GCV) - Mutations in the viral DNA polymerase -> result in cross-resistance to drugs that act directly on DNA polymerase.
What are the characteristics of Foscarnet (phosphonoformic acid) as a viral DNA polymerase inhibitor?
- organic analog of inorganic pyrophosphate
- acts directly on viral DNA polymerase
What are the characteristics of Cidofovir (cytosine; HPMPC) as a viral DNA polymerase inhibitor?
- nucleoside analog with phosphonate group
- in vitro activity against HSV-1, HSV-2, VZV, CMV, EBV, adenovirus, HPV, human polyoma virus.
What are the characteristics of Adefovir (PMEA), tenofovir (PMPA) as a viral DNA polymerase inhibitor?
- Acyclic nucleoside phosphonate
- Activity against retroviruses and HBV.
What are the characteristics of nucleoside analogs as a reverse transcriptase inhibitor?
- Require phosphorylation
- Act as chain terminators of nascent viral DNA
What are the characteristics of non-nucleoside inhibitors as a reverse transcriptase inhibitor?
- Specifically bind non-substrate binding pocket of HIV reverse transcriptase
- Inhibit enzymatic activity
What are assembly inhibitors?
- Protease Inhibitors
- Prevents cleavage of viral proteins by viral protease
- HCV, SARS CoV-2 -> blocks cleavage intracellularly
- HIV -> blocks cleavage after particle release
What are budding/egress inhibitors?
- influenza egress inhibitors
- oseltamivir & zanamivir -> Inhibits neuraminidase to prevent proper release from the host cell
What are cellular proteins?
- IMP Dehydrogenase inhibitors (Ribavirin)
- Inhibits the formation of GTP, which is critical to viral genome formation
