Viral Evasion of the Host Immune Response Flashcards
What is a key difference between internal virus proteins and surface antigens?
Internal viral proteins vary less
Describe the process of presentation of viral peptides on MHC Class I.
Viral peptides are chopped up by the proteasome These peptides are then fed through the TAP protein into the endoplasmic reticulum In the endoplasmic reticulum, it will be loaded onto an MHC class I molecule and it will then move to the cell surface where T cells can recognise the antigen
State three viruses (and the proteins involved) that evade antigen loading onto TAP.
EBV – EBNA1 – this cannot be chopped up by the proteasome
HSV – ICP47 – blocks access of the peptides to the TAP protein
CMV – US6 – blocks ATP binding to TAP
State two viruses (and the proteins involved) that modulate tapasin function and prevent MHC transport.
NOTE: tapasin is involved in loading MHC molecules
Adenovirus E3-19K – prevents recruitment of TAP to tapasin and retains MHC in the ER
CMV – US3 – binds to tapasin and prevents loading of peptides onto MHC
State one virus (and the protein involved) that interferes with MHC presentation at the cell surface.
KSHV (Kaposi Sarcoma Herpes Virus) – kK3 – induces polyubiquitination and internalisation of MHC
What do NK cells recognise on the cell surface that triggers killing of cells?
Missing self – lack of MHC on the cell membrane is not healthy
How do viruses evade this mechanism of NK-mediated killing infected cells?
- Viruses encode MHC analogues (e.g. CMV gp UL40) – virally encoded MHC is useless but it fools the NK cells
- Upregulate MHC
Which cells does HIV target?
CD4+ T cells
Which cells does Ebola kill?
Dendritic cells
Macrophages
T cells (by the bystander response)
In what subset of the population does HCMV (human cytomegalovirus) cause disease?
Immunocompromised. Once infected, the infection is lifelong but is controlled by the immune system. It is re activated when immune system becomes weak
What is the problem with HCMV with regards to bone marrow transplantation?
HCMV infects 60-90% of the population
If HCMV is present in donated bone marrow, it could cause problems in the immunocompromised recipient
What is antigenic drift?
Continued rapid evolution driven by antigenic pressure from the host
What is antigenic shift?
Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.
How else can viruses cause regular infections without changingtheir antigen profile?
They can have several genetically stable serotypes that co-circulate
E.g. rhinovirus has more than 120 antigenically distinct serotypes
How many serotypes of influenza are there?
4
How many serotypes of poliovirus are there and what type of vaccine was produced for polio?
3 – trivalent vaccine
NOTE: one of the serotypes has been eradicated now
How many serotypes of dengue are there?
4
Why do you need to be vaccinated against all 4 dengue serotypes instead of just one?
Antibody dependent enhancement:
Antibody generated against a previous infection (different serotype) can bind to the new serotype but NOT neutralize the virus. Fc receptors on monocytes can then bind to the Ab (bound to antigen). This leads to mass release of cytokines by monocytes (cytokine storm), causing Dengue Haemorrhagic Fever.
What can viruses do to glycoprotein antigens that hinder antibody access to the antigens?
Heavily glycosylate the antigens
What does Ebola viruse have a high content of that makes them appear like apoptotic bodies?
Phosphatidyl serine lipids
What is the benefit to Ebola virus of appearing like apoptotic bodies?
They are rapidly taken up by macropinocytosis and, hence, taken away from antibody surveillance
How does the structure of Ebola affect antibody access to antigens?
Ebola has a long filamentous shape with lots of folds
The folds may make the glycoproteins inaccessible to antibody
Name two factors produced by Ebola that allow it to evade detection by the innate immune system.
VP35
VP24
What important factor does Ebola encode that also helps deal with the antibody response?
Soluble glycoprotein – this acts as an antibody decoy and it is immunosuppressive (inhibits neutrophils)
NOTE: GP2 and retrovirus glycoproteins also have an immunosuppressive peptide
Which virus is only suppressive in macaques?
Reston virus
How does Measles infect cells?
Via SLAM proteins (CD150)
Why did the measles vaccine have a much larger effect on childhood mortality than expected?
Measles can infect memory lymphocytes (these are SLAM positive) and erase immunological memory
So a measles virus infection can result in a 2-3 year decrease in immunological memory that leads to morbidity and mortality from otherdiseases
