Microbiology 1: Interferon Flashcards
Define “interferon”
Soluble cytokine produced when cells are exposed to a virus that stimulates de novo transcription of IF-stimulated genes to cause a cytokine storm
What is the general stimulus for IFN production?
PAMP recognition
What element of a virus acts as a PAMP?
Viral nucleic acid
What sort of PRR is found in the cytoplasm?
Rig-1 like receptors (RLRs)
What sort of PRR is found in endosomes?
Toll-like receptors (TLRs)
Recall the site of production of each subtype of type 1 IFN
IFN-alpha = plasmacytoid dendritic cells IFN-beta = all cells
Recall the TF that leads to the production of each of the subtypes of type 1 IFN
Alpha = IRF7 Beta = IRF3
Where is the IFN-alpha receptor present?
All tissues
Describe the structure of the IFNAR
Heterodimer
Through which receptor does each of the subtypes of tye 1 IFN signal?
IFNAR
Which type of IFN is always first to be made?
Type 1 IFN Beta
What is the function of IFN beta?
Indices anti-viral state i neighbouring cells
Recall the 3 major functions of type 1 IFN
Induce antimicrobial state
Modulate innate immunity
Activate adaptive immunity
How many isotypes are there of each of the subtypes of tye 1 IFN?
IFN alpha has 13
IFN beta has 1
What type of IFN is type2 IFN?
IFN gamma
Through which receptor does IFN gamma signal?
IFNGR
By what sort of cells is IFN gamma produced?
T cells
NK cells
What type of IFN is type 3 IFN?
IFN lambda
Through which receptors does IFN lambda signal?
IL28R amd IL10-beta
Where are IFN-lambda receptors expressed?
Epithelia
What is the main function of IFN lambda?
Protect barriers of body - especially important in liver defence against Hep B/C
Recall the pathway that leads to the transcription of IFN alpha in the presence of RNA viruses
- Virus enters endosome in cell
- PAMP recognition by TLR in endosome
- IFNalpha gene switched on
Recall a protective factor that cells may express against influenza virus?
IFITM3
What is IFITM3?
Prevents virus releasing its genome into the next cell
Recall the pathway that leads to the transcription of IFN beta in the presence of RNA viruses
- RNA recognised by RLR in cytoplasm
- RIG-1 signalls thorugh MAVS on mitochondrion
- IRF3 expressed –> transcription of IFN beta gene
Recall the steps of IFN transcription initiated by DNA viruses
- Sensed in nucleus by cGAS
- cGAS –> cGAMP
- Sting activated
- IFN beta produced
What is the main moderator of the IFN response?
SOCS
What does SOCS stand for?
Suppressor Of Cytokine Signalling genes
Recall 4 examples of ISGs
PKR
2’5’OAS
Mx
ASAR
What is the function of the protein encoded by PKR?
Inhibition of translation (cell’s “altruistic” response)
What is the function of the protein encoded by Mx?
Mx1 inhibits influenza genome
Mx2 inhibits HIV genome
Recall 5 mechanisms of viral evasion of IFN response
- SOCS switched on rapidly
- PAMP concealed
- Rapid replication to outpace response
- IFN blockade
- Gene expression change
How does Hep C evade the viral response?
Produces NS3/4 which can cleave MAVS
How does H1N1 flu evade the T1 IFN response?
Binds RIG-1
How does Ebola evade the T1 IFN response?
Produces VP proteins that block RIG1 and STAT
Recall 3 RNA viruses that can specifically evade T1 IFN
Hep C
Ebola
H1N1 flu
How do DNA viruses tend to evade the T1 IFN response? Give an example of a virus that does this
Encode soluble cytokine receptors to “mop up” IFN eg POX VIRUSES
Recall 4 hopes for therapies utilising IFN
- Mimick Pox virus - produce soluble cytokines
- IFN lambda as an antiviral
- Live attenuated vaccines using viruses that are unable to control IFN
- May be used to treat cancer
Recall the immediate downstream signalling pathway of IFN receptors
Dimerise to activate STAT
