Lec 24 - Viral pathogenesis

Question 1

Define viral pathogenesis

Answer 1

Process occurring when a virus infects a host
Result of complex factors unique to the virus, species and host eg HLA/MHC types, genetics

Question 2

Define disease

Answer 2

Harmful pathologic consequence of normally harmless infection

Question 3

Define virus associated disease

Answer 3

Non-specific or specific prodromal symptoms/signs providing clues to the pathogenic process

Question 4

Define virulence

Answer 4

Relative capacity of a virus to cause disease
More virulent = more disease and more severe disease

Question 5

What is the normal host cell pre-initiation complex and how do viruses alter it?

Answer 5

48S translation preinitiation complex requires polyA tail and 5’ cap
Viruses
- Viral proteases target proteins for degradation
- Viral proteins block subunits forming complex
- Alternative IRES site

Question 6

Compare cap-dependent and picornavirus initiation complex

Answer 6

Cap-dependent (48S complex)
- eIF4E protein binds 5’ cap and complexes with PABP and initiation factors
- Small 40S subunit closest to AUG start codon

Picornavirus initiation complex (IRES)
- Host ITAF binds 5’ UTR’s IRES instead eIF4E
- Terminal VPg protein removed from 5’ end of viral genome so just IRES
- Viral protease degrades eIF4E so no other way of translation

Question 7

How do viruses indirectly turn off translation? Give examples of the 2 viruses that do this

Answer 7

Animal viruses interfere with host transcription by degrading TATA-binding protein (TBP) to prevent host RNA pol 2 forming initiation complex

Poliovirus = 3C protein degrades TBP
HPV = E7 protein binds TBP so it can’t bind

Question 8

Describe the 3 morphological changes viruses can induce in host cells

Answer 8

1. Proliferating membranes = membranes needed for viral replication complexes
2. Syncytia = fusion peptides on cell membranes fuse cells to complete assembly or cell-to-cell spread
3. Rounding and detaching = cell death

Question 9

What enzyme is required for apoptosis? What are the features of apoptosis?

Answer 9

Caspase 3
Features = condensed chromatin, DNA fragmentation, cell shrinking, blebbing

Question 10

What are the triggers for apoptosis? What viruses block these triggers and how?

Answer 10

Triggers = TNF-a or cytochrome c
TNF-a blocked by FLIP and cytochrome c by Bcl-2
HHV-8/Kaposi’s sarcoma virus (KSHV) = FLIP and Bcl-2 homologue
Vaccinia virus = CrmA protein inhibits proteases incl caspase 3

Question 11

Why and how do HPV and HIV activate apoptosis instead of inhibiting it?

Answer 11

Apoptosis releases virions
Both activate caspase 8 which processes caspase 3

Question 12

What is autophagy/xenophagy and how does HIV block it?

Answer 12

Cell engulfs virions/components
HIV’s Nef protein binds Beclin-1 to block its activation in xenophagy

Question 13

What type of viruses are involved in the ER stress response? What is the ER stress response and what are the 3 different pathways? What is the final result of the response?

Answer 13

Enveloped viruses’ transmembrane proteins
ER stress response = misfolding/delayed folding due to volume of translation
1. Slow translation
2. Increased ER folding capacity
3. Increased degradation of unfolded/misfolded proteins
Result = apoptosis if ineffective/prolonged

Question 14

How do anti-viral antibodies inhibit infection?

Answer 14

1. Preventing antigen binding (neutralisation)
2. Tagging pathogen for immune destruction (opsonisation)
3. Activating complement cascade