Flashcards in Interferon Deck (53)
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
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.
Vif – APOBEC
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