What evolutionary pressure is on viruses?
Development of strategies to escape the immune system for sufficient time to replicate and reinfect
What evolutionary pressure is on the immune system?
Development of multiple strategies to clear an infection but without causing unnecessary damage to host tissue
What four things can a cell do when it encounters a pathogen?
1) Clear the pathogen by phagocytosis 2) Present the antigen to the adaptive immune system 3) Alert and attract immune cells 4) Kill itself
Outline the basic activation of the innate immune system
1) Pathogen associated molecular pattern recognised 2) Signalling cascade to activate transcription factors 3) Transcription of anti-virulent factors, adaptive immune system recruitment molecules and apoptotic factors (also negative regulators of immunity to control the response)
Outline the downstream actions of IRF
IRF3 and 7 are activated by PRR and induce transcription of IFNß and IFNα (type 1 interferons). Type1 IFN’s cause transcription of interferon stimulated genes (ISGs) and bind the interferon A receptor which induces a second wave interferon stimulated genes via IRF and STAT
What are the functions of type 1 IFN’s in the immune system?
- Inhibit protein translation in the cell - so virus cannt replicate
- Induce cell death
- Activate innate immune system (e.g. NK celss)
- Activation of antigen presenting machinery
How can viruses escape IFN response?
- Interfere with PRR sensing
- Interfere with signalling downstream of PRR
- Encode decoy IFN A receptor
- Encode decory IRF receptor
- Suppress activity of ISGs
How does influenza stop IFN activity?
NS1 protein binds to dsRNA and sequesters it from PRR
Also inhibits PKR - a kinase in the downstream from PRR
How does Karcosa-sarcoma herpes virus inhibit IFN immune response?
Inhibits IRF by having its own version of IRF which can outcompete cellular IRF
How Hepatitis C stop IFN immune activity?
NS3-NS4 protease is used to cleave signalling molecules, TRIF and MAVS,
NS5A inhibits PKR
What else if NS3-NS4 used for?
Cleaving protein products important for virus replication
How Hepatitis B stop IFN immune activity?
HBX causes degradation of MAVS
What other proteins will NS1 inhibit?
RIG-1, PKR and OASL
How can viruses escape apoptosis?
- Inhibition of IFN response
- Inhibition of TNF receptor
- Inhibition of caspases
- Inhibition of p53
- Encode for pro-survival genes
What is a possible result of inhibition of p53?
Which virus’ are known for this?
Cancer
HPV - E6/E7 protein
KSHV - vGPCR
When was the first tumour inducing virus found?
What was it?
1964
EBV virus causes Burkitt’s lymphoma
Which is the only transmissible cancer cell?
Canine transmissible venereal tumour
How can viruses escape antigen presentation?
- Down-regulate MHC class 1
- Inhibit proteosome
- Inhibit transport to cell membrane
What antiviral activities do antibodies have?
- Antibody-dependent cytotoxitcity
- Complement activation
- Antibodies for viral glycoprotein
How can virus escape antibody acitivity?
- Inhibitition of NK’s
- Inhibition of complement
- Mutation of envelope proteins
- Directing antibodies to irrelevant epitopes on envelope
Which receptor is supressed during KSHV?
Why is it surpressed?
TLR4
TLR4 mediates innate immune response against KSHV
What disease can you develop if you have mutant TLR4?
Multicentric Castleman’s Disease
A lymphoma on top of KSHV
How was TLR4 initially shown to be affected by KSHV?
TLR4 was the only toll-like receptor which had lower mRNA levels during KSHV infection
What effect does UV treatment have on viruses?
DNA damage - so the virus can infect but can’t replicate
