banfield lecture 10/11

Question 1

what defence does hepatitis C have against the IFN system?

Answer 1

it encodes a protease called NS3 which cleaves intermediate adapter molecules.

In the Tl3 receptor pathway it cleaves Trif

In the RIG-I and mda5 pathways it cleaves TM.

Question 2

how does pox virus evade the IFN system?

Answer 2

it produces a compound called B18R which is an extracellular IFN receptor. this binds IFN so there is none to binds TLR’s . B18R sometimes called a sponge

Question 3

explain how some viruses evade IFN system by targeting the JAK kinases.

Answer 3

some viruses can produce something that binds and inhibits the JAK kinase. The kinase becomes inactivated

Question 4

explain how some viruses target the STAT proteins to stop IFN system.

Answer 4

1. some viruses can produce a molecule that binds to the STAT TF’s and inhibits phosphorylation
2. some viruses can produce proteases that will degrade STAT TF’s
3. some pox viruses can make a phosphotase which removes the phosphate group on the STAT dimer which inactivates it.

Question 5

How do some viruses target the IFR9 - STAT complex to evade the IFN system?

Answer 5

some viruses can form a protein which blocks the formation of the ISGF3 complex (stat + IFR9). this can be the same protein that stops STAT from dimerizng

Question 6

Probs dont need to know but its here:
what does
Polyomavirus do?

Answer 6

binds and inactivates JAK1

Question 7

Probs dont need to know but its here:
what does
Sendai virus C do?

Answer 7

blocks STAT phosphorylation

Question 8

Probs dont need to know but its here:
what does
simian virus 5 do?

Answer 8

makes a protease that degrades STAT 1

Question 9

Probs dont need to know but its here: 
what does 
vaccina virus (pox virus) do?

Answer 9

makes a phosphatase that de-phosphorylates the STAT dimer

Question 10

Probs dont need to know but its here: 
what does 
hepatitis C (other than cleaving adapter intermediates) do?

Answer 10

stops the formation of ISGF3 –> the STAT + IFR9 duo.

Question 11

Once in the antiviral state, what occurs with the PKR system if a virus infects the cell (start from IFN binding, i.e. getting to antiviral state)

Answer 11

1. IFN binds the cell
2. JAK/STAT system signals for ISG transcription
3. translation of transcript produces many proteins including PKR
4. PKR chills in an activated state waiting for infection
5. Cell is infected. The PKR protein must bind dsRNA to become activated!
6. Active PKR phosphorylates (which turns off) eIF-2 which is an important TF. this leads to the Cessation of Gene expression and protein
7. along with other events, Apoptosis occurs

Question 12

aside from apoptosis, inhibition of protein synthesis also prevents new virus production in that cell, t of f?

Answer 12

true

Question 13

what does PKR bind too?

Answer 13

dsRNA

Question 14

how does herpes virus stop PKR action?

Answer 14

it brings a phosphatase to eIF-2. Everytime PKR phosphorylates (inactivates) eIF-2, this herpes kinase will take the P group off and reactivate it

Question 15

t or f, there is a balance between IFN success and viral evasion

Answer 15

true. sometimes IFN is produced properly and PKR works correctly, sometimes IFN is inhibited or PKR is ineffective.