12 Viruses vs Host cell – interferon response

Question 1

what is innate immunity from

Answer 1

non-specific, all antigens attacked equally. Genetically based, pass to offspring

Question 2

what is adaptive immunity from

Answer 2

develops when exposed to various antigens and builds defence that is specific to antigen

Question 3

what are the nonspecific defences

Answer 3

anatomic barriers, inhibitors, phagocytosis, fever, inflammation, and IFN

Question 4

what are the specific defences

Answer 4

antibody and cell-mediated immunity

Question 5

what are the properties of interferon

Answer 5

• cytokines
• induction is rapid and transient
• bind to receptors (IFN receptors) then cause signal transduction cascade-inducing cytokine and antiviral state – some viruses are sensitive, and some are resistant to IFN

Question 6

what are very sensitive to interferon

Answer 6

VSV

NDV

Question 7

what are very resistant to interferon

Answer 7

influenza

HSV

Question 8

what is a signal transduction cascade

Answer 8

signal from outside cell binds to receptor and turns on transcription genes

Question 9

what are interferons released as

Answer 9

soluble factor from virally infected tissues

Question 10

what do interferons do when released

Answer 10

protect neighbouring cells from infection

Question 11

when do cells synthesis IFNs

Answer 11

when activated by IFN-inducing agent

Question 12

what is an IFN-inducing agent

Answer 12

virus most common

Question 13

what are the major biological actions of interferons

Answer 13

• induce class I and II MHC antigens
• activate monocytes/macrophages, NK, cytotoxic T cells
• modulation of Ig synthesis in B cells
• induction of Fc receptors in monocytes
• inhibition of growth of non-viral intracellular pathogens
• pyrogenic action (fever)

Question 14

what does the interferon system do

Answer 14

Cellular mechanism to limit virus infection to first infected cell
Is a cytokine (IFN) binds to front receptor on the host cell receptor activates other proteins that turn on genes – interferon stimulated genes

Question 15

what do all interferon stimulated genes have in common

Answer 15

have in their promoter interferon stimulated response element in their nucleus

Question 16

what does PRR recognise

Answer 16

dsRNA

Question 17

how do interferons induce antiviral state

Answer 17

Interferon released into second cell
Interferon bind to interferon receptor on outside of the cell
Signal transduction – IFN goes from outside of the cell and induces interferon stimulated genes
Genes are activated and suppresses viral replication

Question 18

what does PKR do

Answer 18

stops translation – inhibition of protein synthesis

Question 19

what does OAS do

Answer 19

degrade mRNA

Question 20

what is STAT

Answer 20

Signal transductor and activator of transcription

Question 21

what turns on transcription

Answer 21

STAT1-STAT2 travel from cytoplasm to nucleus = turn on transcription

Question 22

what does virus induce

Answer 22

ISGs – interferon stimulates genes (cell is in ‘antiviral state’)

Question 23

what happens when virus is induces ISGs

Answer 23

New virus comes in and activates
PKR binds
OAS made
Shutting down protein synthesis by degrading mRNA and blocking translation

Question 24

how does PKR block translation

Answer 24

Will trap eIF2B and block translation

As at the end of translation eIF2 needs to be changed from GDP to GTP

Question 25

how are virus infected cells translationally controlled

Answer 25

- viral messages are translated while cellular messages are not - mechanism whereby lytic or fast-growing viruses take over cell for own benefit, hijack translational machinery - adenovirus eIF2-alpha (VA RNA) and eIF4F (TPL)

Question 26

what blocks the initiation of eIF2-GDP

Answer 26

PKR

Question 27

how does PKR phosphorylate the eIF2-GDP

Answer 27

PKR dimerizes (2 subunits) on dsRNA molecule – phosphorylates each other and eIF2

Question 28

what does VA RNA, TAR and EBERS bind to

Answer 28

monomers not dimers

Question 29

why can VA RNA, TAR and EBERS not bind to dimers

Answer 29

Viruses make short RNA | Bind PKR monomers and cause dimerization

Question 30

what makes VA RNA

Answer 30

adenovirus

Question 31

what makes EBERS

Answer 31

EBV

Question 32

what makes TAR

Answer 32

HIV

Question 33

what are the mechanisms involving prevention of dimers - HCV

Answer 33

HCV encodes a protein NS5A – binds to PKR

Question 34

what are the mechanisms involving prevention of dimers - FLU

Answer 34

activates cellular inhibitor which recruits heat shock protein 70

Question 35

what are the mechanisms involving prevention of dimers - involving PKR

Answer 35

mechanisms involving PKR expression/stability

Question 36

what are the mechanisms involving prevention of dimers - involving dsRNA

Answer 36

mechanisms involving sequestering dsRNA

Question 37

what are the mechanisms involving prevention of dimers - involving substrate

Answer 37

mechanisms involving substrate interaction

Question 38

how do viruses block PKR

Answer 38

- block dimerization (bind dsRNA, Protein) - block phosphorylation of eIF2 (pseudosubstate) - degrade PKR (brute force) - sequester dsRNA (keeps activator away)

Question 39

translational control, regulation of eIF4E phosphorylation

Answer 39

- eIF4F remains dephosphorylated in adenovirus infected cells inactivated cap binding protein - eIF4E and cap binding complex (4F) scanning cellular translation stopped – displacement of - eIF4G associated MnK kinase thus host translation shut off

Question 40

what does the adenovirus late transcripts (L1-5) tripartite leader do

Answer 40

employs ribosome shunting method to translate cap independently

Question 41

what makes coat proteins

Answer 41

Adenovirus late messages

Question 42

what allows cap independent translation

Answer 42

Have a little RNA segment

Question 43

what does the ribosome shunt do

Answer 43

binds near cap-(At TPL) but scans short sequence then jumps secondary structure to AUG