Hale - interferon Flashcards
What are the three roles of IFN response ?
Directly put cells in an antiviral state.
Recognise the infection and signal neighboring cells.
Prime the cellular immunity.
How was interferon discovered ?
inactivated IAV infection of egg cells, incubated overnight. Supernatant transferred gave protection to live IAV.
What are symptoms of IFN response ?
Fever chills nausea and malaise.
Give 2 examples of recognised PAMPs.
Cytosolic DNA or dsRNA.
What senses cyotplasmid DNA ?
cGAS.
What’s the name of the receptors localised in membranes (plasma or endosomal) ?
TLRs.
Give an example of a: PAMP Sensor Adaptor Signalling Kinase IFN Transcription Factor
In the context of an RNA virus
PAMP : dsRNA Sensor : RIGI MDA5 Adaptor: MAVS Kinases: TBK1 TF: IRF3/7 or NFKb.
Give an example of a: PAMP Sensor Adaptor Signalling Kinase IFN Transcription Factor
In the context of an DNA virus
PAMP : cytosolic DNA Sensor : cGas Adaptor: STING Kinases: TBK1 TF: IRF3 or NFKb.
What’s an IFN receptor ?
Heterodimeric proteins at the cell surface, whose intracellular bits are associated with the signaling kinases such as the Jak and the Tyks.
Give the interferon pathway (basic)
IFN binds to an IFNAR. Jak/Tyk transduce the signal by phosphorylating STAT1/2m which binds IRF9. Translocates to the nucleus, expresses ISGs.
What are IFITMs and how 7 when do they act?
IFITMs are transmembrane proteins of the endosome that act before the virus fuses with the membrane by making the membrane more rigid, resulting in an abortive infection.
Do all IFITMs inhibit the same viruses ?
No: IFITM1 inhibits potently HIV1 but 2 and 3 do IAV etc.
What’s the deal with MxA and tropism ?
Human MxA is potent against avian viruses - but not against human IAV: NP proteins were host-adapted to survive it.
What’s PKR’s role ?
It gets phosphorylated after detection of dsRNA, then phosphorylates the eIF2a GF to render it inactive which shuts down translation.
What’s the role of tetherin ?
Holds fully formed enveloped viruses on the cell to prevent budding.
Give three examples of viral interferon antagonists.
NS1 (haha)
K3L protein (decoy substrate for PKR)
ICP34.5 (Herpes, uses PP1) dephosphorylates eIF2a.
What’s NS1 implication for disease and host adaptations?
If you take an avian virus and you stick the human Ns1 residues on it, mortality explodes.
What’s the 3 phenotypes for IFN responses seen in COVID patients?
Early robust IFN response, causing virus to be cleared quickly.
Delayed IFN; more difficult to control.
Deficiency: viral load uncontrollable.
IFN autoantibodies: how do they come about?
pre existing and increase with age: might explain partially severity of the Rona with old folks.
What’s the story of that boy who got the MMR vaccine and got reaaaally sick?
Basically, his cells were super suceptible to viral infections and IFN treatment was doing nothing: turns out, he had a single mutation that caused his STAT2 levels to be undetectable.
What’s the IFITM3 SNP ?
Its a single nucleotide polymorphism causing it to become inactive: patients that have this version are wayyy overrepresented in the hospitalised with IAV group.
Give a couple extra examples of anti RNA ISGs
OAS, RNaseL.
What IFN type target mostly IAV and SARS? Rotavirus ? RSV?
Type I -> IAV and SARS
Type 3 -> Rotavirus
RSV - type 1 and 3.
what are ISRE?
Interferon Sensitive Response Domains.
