Mid 1: Lec 9

Question 1

Interferon types and main subtypes

Answer 1

Type I: mainly alpha

Type II: mainly gamma

Type III: mainly lambda

Question 2

Interferon general effects

Answer 2

antiviral, growth inhibition, immunosurveillance for malignant cells

Question 3

IFN I and II receptor structure and associated proteins

Answer 3

multichain structures

-I:
IFNAR1 subunit associated with TYK2
IFNAR2 subunit associated with JAK1

-II:
IFNGR1 subunit associated with JAK1
IFNGR2 subunit associated with JAK2

Question 4

IFN I activation pathway

Answer 4

IFN I ligand (e.g. IFN alpha) binds IFN I

autophosphorylation and activation of JAK 1 and TYK1 which regulate the phosphorylation and activation of STATs 1, 2, 3, 5

STATS form homo/hetero dimers and translocate to nucleus to act as transcription factors on ISGs (interferon stimulated genes)

Question 5

STAT 4, 6

Answer 5

activated only in certain cells types like endothelial or lymphoid cells

Question 6

ISGF3 complex (inc: what is phosphorylated, what is not)

Answer 6

ISG factor 3

composed of phosphorylated STAT 1 and STAT 2 and unphosphorylated IRF9

the complex binds IFN stimulated response elements (ISREs) which are part of promotors of certain ISGs. This initiates transcriptiond

Question 7

GAS elements and ISREs

Answer 7

Some ISGs have only GAS or ISRE, some have both

-GAS:
IFN-Gamma activated site

sequences in ISG promotors that are bound by IFN II STAT complexes

-ISREs:

Interferon stimulated response elements

regions of ISGs bound by IFN I induced STAT complexes

Question 8

CRKL path

Answer 8

IFN binds IFN I, CRKL binds tyk2 and is phosphorylated, CRKL binds STAT5 which is also phosphorylated, CRKL-STAT5 complex translocates to nucleus and binds a GAS of ISG

CRKL also results in GEF (guanine nucleotide exchange factor) activity of C3G, C3g regulates guanine nucleotide exchange of RAP1 (G-protein) which may promote growth inhibition

Question 9

Label canonical interferon receptor path

Question 10

Viral infection types (with regards to clearance), relation to IFNs

Answer 10

-Viral levels
sustained: stays at 0
transient: reaches goes to 0 and back multiple times
persistent: won’t go to 0
-Different IFN types are present at different levels during different stages of infection. Type I alone is not enough to clear HCV virus.

Question 11

examples of viruses that can evade and persist

Answer 11

Hep B, Hep C, HIV

Question 12

Lamers et al: technique, findings

Answer 12

3d organoids of intestinal crypts used

gut enterocytes can be resovoirs for covid but are non-productive therefore there is not much risk of catching covid from fecal matter

Increased covid levels leads to increased expression of IFN regulated genes