Micro 5: Viral evasion of host immunity Flashcards
How can the immune system detect viruses
Viruses are intracellular pathogens and so their proteins are easy targets for processing and presentation by MHC.
What parts of the virus is an immune response mounted against
The MHC can present all parts of the viruses, not just the outside. The antibodies will be made obviously to surface molecules But the inside of the virus can be preseted on MHC and this can trigger CD8+ T cell to kill the virally infected cell
What is more variable, internal viral proteins or surface molecles?
Internal viral proteins can be targets of cellular immunity. They tend to vary less than surface antigens.
T/F a virus can be chronic without interfering with cellular immuity
F… Viruses that persist must evade cellular immunity
Give an example of a family of viruses that evade cellular immunity
. The family of herpes viruses are the classic examples.
Outline presenation of internal peptides inside a cell
Proteins in cell chopped up by proteosome, peptides transported into the ER where they are loaded onto MHC class 1 and the b2-microglobulin is added This is then transported through the golgi apparatus and displayed on the surface of the cell The peptide being presented can then be seen by a T cell receptor on a T lymphocyte
Which cells in th ebody expresses class 1 MHC
Both
What activates the T cell
The MHC 1, TCR, foreign peptide and CD8 is important too
How do HSV 1 prevent interfere with cellular immunity
HSV ICP47 blocks access of the processed peptide to TAP
How does EBV evade cellular immunity
EBV EBNA1 cannot be processed by the proteasome so the viral protein cannot be chopped up and put into the ER so it cannot be presented in MHC class 1 to activate T cell
What is the name of the protein that transports peptides into the ER
TAP
How does CMV evade cellular immunity
CMV US6 stops ATP binding to TAP preventing translocation .CMV US3 binds tapasin and prevent peptides being loaded to MHC (i.e. cuts off the energy to TAP so peptides can’t get into the ER and thus cannot be associated with the MHC molecules and cannot be presented to the T cells)
Which molecule assists in loading the peptide onto the MHC
Tapasin
How can adenovirus effect cellular immnity
Adenovirus E3-19K prevents recruitment of TAP to tapasin and also retains MHC in the endoplasmic reticulum
How does the KSHV (HHV8) evade cellular immunity
KSHV kK3 protein induces polyubiquitinylation and internalization of MHC. From the internalized endosome, MHC is passed to lysosomes where it is degraded. Cannot present viral proteins to the T cell
What type of virus is the HPV
DNA virus, but with shorter genome than herpes
How does HPV evade the immune response
Both cellular and innate response Just note that because HPV has a small genome, its proteins often do diverse range of functions E6/E7 are oncogenic (interfere with cell cycle), but they are also binding to proteins involved in the interferon detection pathway (cGAS, STING etc) and the IFN-a effector pathway (innate). E7 also prevents transcription of MHC and TAP proteins E5 holds onto the MHC class 1 molecule in the ER and the golgi and prevents it from being transported to the surface (cellular)….. BUT think about the consequence of loss of MHC
What is the human response to lack of MHC on cells
This makes immune system think there is virus in the cell So loss of MHC1 activates NK cells Normal healthy cells display MHC at their surface. Cells that don’t display MHC are detected by NK cells and killed. Viruses that disrupt MHC presentation would end up being killed by NK cells.
How do viruses get around the NK response which kills them if they interfere with MHC Give an example
Viruses encode MHC analogues (CMV gpUL40) or upregulate MHC.
What are virus vaccines usually trying to achieve
An antibody response
What is antigenic drift, vs antigenic shift
Continued rapid evolution driven by antigenic pressure from the host= antigenic drift Introduction of new subtypes from animal source= antigenic shift
Give example of antigenic drift and shift
Drift: influenze antigenic drift Shift: influenza antigenic shift
Outline the conservation of haemagluttinin
There are some AAs which are highly conserved and some which are highly variable between different haemagglutinin molecules The head domain (which pokes out most into the external environment) is highly variable
Why is the head domain likely to be variable in the haemagglutinin molecule
So that the B cells don’t mount an immune response to it (i.e. the AA are constantly changing so that previously formed ABs cannot bind them) =ESCAPE. This is the basis of antigenic drift
What is the head resonsible for in haemagluttinin
Binding to the cells influenza wants to infect (i.e. respiratory epithelium) The target of B cells to make antibodies against it =HA1
How much do AAs have to change within the haemagglutinin molecule in order to prevent preformed AB binding
If the haemagglutinin has only a couple of AAs change, it will escape the preformed antibodues
Which part of the haemagluttinin has conserved AAs and why
The stalk (=HA2) Maybe because the protein is so critical to the virus that it cannot be varied (not selected for) OR no evolutionary pressure yet (only a tiny fraction of the antibodies actually see the stalk, they se the head)
How could a universal influenza be developed
Develop AB to the part of the haemagglutinin which is conserved and integral to its function and thus present on every haemagglutinin thus alowing us to target every strain of influenza
