12 Viruses vs Host cell – interferon response Flashcards
what is innate immunity from
non-specific, all antigens attacked equally. Genetically based, pass to offspring
what is adaptive immunity from
develops when exposed to various antigens and builds defence that is specific to antigen
what are the nonspecific defences
anatomic barriers, inhibitors, phagocytosis, fever, inflammation, and IFN
what are the specific defences
antibody and cell-mediated immunity
what are the properties of interferon
- 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
what are very sensitive to interferon
VSV
NDV
what are very resistant to interferon
influenza
HSV
what is a signal transduction cascade
signal from outside cell binds to receptor and turns on transcription genes
what are interferons released as
soluble factor from virally infected tissues
what do interferons do when released
protect neighbouring cells from infection
when do cells synthesis IFNs
when activated by IFN-inducing agent
what is an IFN-inducing agent
virus most common
what are the major biological actions of interferons
- 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)
what does the interferon system do
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
what do all interferon stimulated genes have in common
have in their promoter interferon stimulated response element in their nucleus
what does PRR recognise
dsRNA
how do interferons induce antiviral state
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
what does PKR do
stops translation – inhibition of protein synthesis
what does OAS do
degrade mRNA
what is STAT
Signal transductor and activator of transcription
what turns on transcription
STAT1-STAT2 travel from cytoplasm to nucleus = turn on transcription
what does virus induce
ISGs – interferon stimulates genes (cell is in ‘antiviral state’)
what happens when virus is induces ISGs
New virus comes in and activates
PKR binds
OAS made
Shutting down protein synthesis by degrading mRNA and blocking translation
how does PKR block translation
Will trap eIF2B and block translation
As at the end of translation eIF2 needs to be changed from GDP to GTP
how are virus infected cells translationally controlled
- 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)
what blocks the initiation of eIF2-GDP
PKR
how does PKR phosphorylate the eIF2-GDP
PKR dimerizes (2 subunits) on dsRNA molecule – phosphorylates each other and eIF2
what does VA RNA, TAR and EBERS bind to
monomers not dimers
why can VA RNA, TAR and EBERS not bind to dimers
Viruses make short RNA
Bind PKR monomers and cause dimerization
what makes VA RNA
adenovirus
what makes EBERS
EBV
what makes TAR
HIV
what are the mechanisms involving prevention of dimers - HCV
HCV encodes a protein NS5A – binds to PKR
what are the mechanisms involving prevention of dimers - FLU
activates cellular inhibitor which recruits heat shock protein 70
what are the mechanisms involving prevention of dimers - involving PKR
mechanisms involving PKR expression/stability
what are the mechanisms involving prevention of dimers - involving dsRNA
mechanisms involving sequestering dsRNA
what are the mechanisms involving prevention of dimers - involving substrate
mechanisms involving substrate interaction
how do viruses block PKR
- block dimerization (bind dsRNA, Protein)
- block phosphorylation of eIF2 (pseudosubstate)
- degrade PKR (brute force)
- sequester dsRNA (keeps activator away)
translational control, regulation of eIF4E phosphorylation
- 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
what does the adenovirus late transcripts (L1-5) tripartite leader do
employs ribosome shunting method to translate cap independently
what makes coat proteins
Adenovirus late messages
what allows cap independent translation
Have a little RNA segment
what does the ribosome shunt do
binds near cap-(At TPL) but scans short sequence then jumps secondary structure to AUG
