Hale - interferon

Question 1

What are the three roles of IFN response ?

Answer 1

Directly put cells in an antiviral state.
Recognise the infection and signal neighboring cells.
Prime the cellular immunity.

Question 2

How was interferon discovered ?

Answer 2

inactivated IAV infection of egg cells, incubated overnight. Supernatant transferred gave protection to live IAV.

Question 3

What are symptoms of IFN response ?

Answer 3

Fever chills nausea and malaise.

Question 4

Give 2 examples of recognised PAMPs.

Answer 4

Cytosolic DNA or dsRNA.

Question 5

What senses cyotplasmid DNA ?

Answer 5

cGAS.

Question 6

What’s the name of the receptors localised in membranes (plasma or endosomal) ?

Answer 6

TLRs.

Question 7

Give an example of a:
PAMP
Sensor
Adaptor
Signalling Kinase
IFN Transcription Factor

In the context of an RNA virus

Answer 7

PAMP : dsRNA
Sensor : RIGI MDA5
Adaptor: MAVS
Kinases: TBK1
TF: IRF3/7 or NFKb.

Question 8

Give an example of a:
PAMP
Sensor
Adaptor
Signalling Kinase
IFN Transcription Factor

In the context of an DNA virus

Answer 8

PAMP : cytosolic DNA
Sensor : cGas
Adaptor: STING
Kinases: TBK1
TF: IRF3 or NFKb.

Question 9

What’s an IFN receptor ?

Answer 9

Heterodimeric proteins at the cell surface, whose intracellular bits are associated with the signaling kinases such as the Jak and the Tyks.

Question 10

Give the interferon pathway (basic)

Answer 10

IFN binds to an IFNAR. Jak/Tyk transduce the signal by phosphorylating STAT1/2m which binds IRF9. Translocates to the nucleus, expresses ISGs.

Question 11

What are IFITMs and how 7 when do they act?

Answer 11

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.

Question 12

Do all IFITMs inhibit the same viruses ?

Answer 12

No: IFITM1 inhibits potently HIV1 but 2 and 3 do IAV etc.

Question 13

What’s the deal with MxA and tropism ?

Answer 13

Human MxA is potent against avian viruses - but not against human IAV: NP proteins were host-adapted to survive it.

Question 14

What’s PKR’s role ?

Answer 14

It gets phosphorylated after detection of dsRNA, then phosphorylates the eIF2a GF to render it inactive which shuts down translation.

Question 15

What’s the role of tetherin ?

Answer 15

Holds fully formed enveloped viruses on the cell to prevent budding.

Question 16

Give three examples of viral interferon antagonists.

Answer 16

NS1 (haha)
K3L protein (decoy substrate for PKR)
ICP34.5 (Herpes, uses PP1) dephosphorylates eIF2a.

Question 17

What’s NS1 implication for disease and host adaptations?

Answer 17

If you take an avian virus and you stick the human Ns1 residues on it, mortality explodes.

Question 18

What’s the 3 phenotypes for IFN responses seen in COVID patients?

Answer 18

Early robust IFN response, causing virus to be cleared quickly.
Delayed IFN; more difficult to control.
Deficiency: viral load uncontrollable.

Question 19

IFN autoantibodies: how do they come about?

Answer 19

pre existing and increase with age: might explain partially severity of the Rona with old folks.

Question 20

What’s the story of that boy who got the MMR vaccine and got reaaaally sick?

Answer 20

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.

Question 21

What’s the IFITM3 SNP ?

Answer 21

Its a single nucleotide polymorphism causing it to become inactive: patients that have this version are wayyy overrepresented in the hospitalised with IAV group.

Question 22

Give a couple extra examples of anti RNA ISGs

Answer 22

OAS, RNaseL.

Question 23

What IFN type target mostly IAV and SARS? Rotavirus ? RSV?

Answer 23

Type I -> IAV and SARS
Type 3 -> Rotavirus
RSV - type 1 and 3.

Question 24

what are ISRE?

Answer 24

Interferon Sensitive Response Domains.