Inteferon: part 3

Question 1

What type of virus are Pox and Herpes viruses?

Answer 1

Large DNA viruses

Question 2

What do Pox viruses encode that helps deal with the interferon response?

Answer 2

They encode soluble cytokine receptors that mop up IFN and prevent it from reaching its receptors

Question 3

Describe a potential therapeutic use of viruses encoding soluble cytokine receptors to help deal with the interferon response

Answer 3

This could be useful in autoimmune or inflammatory conditions where IFN and other cytokines are produced in abundance

Question 4

Name two proteins produced by HIV that helps deal with restriction factors and state what they target.

Answer 4

Vif – APOBEC Vpu – Tetherin

Question 5

Describe the normal action of APOBEC.

Answer 5

APOBEC is involved in the innate immune resistance to retroviruses and hepadnaviruses APOBEC modifies some of the nucleotides in reverse transcription and makes them into the wrong version APOBEC deaminates dC to dU in the minus strand of viral cDNA during reverse transcription This leads to G to A hypermutation resulting in ERROR CATASTROPHE This results in so many mutations that the viral genome becomes nonsense and the virus can’t replicate

Question 6

What is the effect of Vif on APOBEC?

Answer 6

Vif counteracts the activity of APOBEC and targets it for degradation This removes the interference of APOBEC with reverse transcription

Question 7

Describe the normal action of tetherin.

Answer 7

Tetherin sits on the cell surface of infected cells and binds to viruses that try to escape the cell to go and infect other cells This limits the spread of viral infection

Question 8

What is the effect of Vpu on tetherin?

Answer 8

Vpu pulls tetherin back from the cell surface and targets it for degradation

Question 9

What are two proteins produced by Ebola virus that are particularly important in dealing with the immune response?

Answer 9

VP35 VP24

Question 10

What do VP35 and VP24(proteins produced by Ebola virus that important in dealing with the immune response) do?

Answer 10

VP35 – inhibits the RIG-I pathway VP24 – stops the signal getting through from the IFN beta receptor to the nucleus (stops the STAT1 molecule from getting to the nucleus)

Question 11

What two techniques can be used to observe the skewing of the immune response by viruses?

Answer 11

Transcriptomimics – shows changes in mRNA production Proteomimics – shows changes in protein expression

Question 12

Describe how viral infections can cause cytokine storm.

Answer 12

Lots of virus propagation –> lots of interferon being produced –> massive release of TNF alpha and other cytokines

Question 13

What is a serious consequence of cytokine storm?

Answer 13

Pulmonary fibrosis – due to accumulation of immune cells in the lungs

Question 14

Explain why viruses that cannot control the interferon can beused as the next generation of live attenuated vaccines.

Answer 14

They will be able to infect the cells and it will replicate sufficiently to be able to mount an immune response but it wont replicate to the extent where it causes disease

Question 15

The downside of this feature of the viruses is that these virus particles can’t be propagated in normal healthy cells. What is the solution to this issue?

Answer 15

Propagate the viruses in cells that are deficient in the IFN response

Question 16

Explain why interferons are not frequently used as an antiviral therapy.

Answer 16

They stimulate the production of several cytokines and this causes several unpleasant side effects

Question 17

What disease is IFN used to treat?

Answer 17

Hepatitis C (a combination of pegylated IFN is used with ribavirin

Question 18

Explain the reasoning behind using IFN-lambda as a treatment for influenza.

Answer 18

Receptors for IFN lambda are only found on epithelial surfaces (the site of infection of influenza is respiratory epithelium) IFN lambda cannot signal through immune cells and cause immunopathology It will only induce an antiviral state in the epithelial cells

Question 19

Explain how oncolytic viruses would work.

Answer 19

Viruses are engineered that can uniquely replicate in tumour cells and kill them Generally speaking, cancer cells are deficient in their ability to mount a proper interferon response So, a virus that is unable to control the IFN response will NOT be able to replicate in normal healthy cells but they will be able to infect and replicate in cancer cells