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 HMCV (human cytomegalovirus) cause disease?
Immunocompromised
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
Explain how our knowledge about HCMV has allowed improved medical outcomes in bone marrow transplantation.
HCMV encodes UL138, which leads to loss of MRP-1 from the infected cell surface
MRP-1 is a transporter of toxic drugs out of the cell
Loss of MRP-1 leads to accumulation of certain molecules in the infected cell
Vincristine is a toxic drug that accumulates in the infected cells and kills them
So treating donated cells with vincristine before the transplant can eliminate CMV
What is antigenic drift?
Continued rapid evolution driven by antigenic pressure from the host
What is antigenic shift?
Introduction of new subtypes of the virus from an animal source
NOTE: when they come from an animal source, the antigens don’t look like anything that humans have seen before
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
