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Y2 MCD - Microbiology - Laz DC > Interferon > Flashcards

Flashcards in Interferon Deck (53)
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Name a family of genes that suppress the cytokine signalling and turn off the response.



State some mechanisms of viral evasion of the IFN response.

Avoid detection by hiding the PAMP
Interfere globally with host cell gene expression and/or protein synthesis
Block IFN induction cascades
Inhibit IFN signalling
Activate SOCS
Replication strategy that is insensitive to IFN


Explain how hepatitis C controls the interferon response.

This is a protease that cleaves MAVS
MAVS is important in detecting Hep C through the RIG-I pathway
So Hep C is not detected


Explain how influenza controls the interferon response.

Acts an antagonist to interferon induction by binding to the RIG-I/TRIM25/RNA complex and preventing activation of the signalling pathway
It also prevents nuclear processing of newly induced genes
NS1 also migrates to the nucleus where it prevents the export of newly synthesised genes


What type of virus are Pox and Herpes viruses?

Large DNA viruses


What do Pox viruses encode that helps deal with the interferonresponse?

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


Describe a potential therapeutic use of this feature

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


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

Vpu – Tetherin


Describe the normal action of APOBEC.

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


What is the effect of Vif on APOBEC?

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


Describe the normal action of tetherin.

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


What is the effect of Vpu on tetherin?

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


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



What do these proteins do?

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)


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

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


Describe how viral infections can cause cytokine storm.

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


What is a serious consequence of cytokine storm?

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


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

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


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?

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


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

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


What disease is IFN used to treat?

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


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

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


Explain how oncolytic viruses would work.

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