Viral evasion of host immunity

Question 1

Explain how viruses act as targets

Answer 1

Viruses are intracellular pathogens and so their proteins are easy targets for processing and presentation by MHC
Internal viral proteins can be targets of cellular immunity. They tend to vary less than surface antigens.

Question 2

Give examples of viruses that evade cellular immunity and therefore persist

Answer 2

The family of herpes viruses

Question 3

Give a summary of viruses and their replication

Answer 3

obligate intracellular parasites. A virus hijacks host cells’ production systems to replicate its genome (which can be DNA or RNA) and then produce the necessary proteins for more viral particles to be made, packaged, and released.

Question 4

Describe the structure of a virus

Answer 4

Lipid envelop
Protein capsid
(both)

Question 5

What are the stages of defence against viruses

Answer 5

intrinsic defences
innate immunity
acquired immunity.

Question 6

Describe the Viral regulation of MHC class I

Answer 6

-

Question 7

Explain how viruses cause evasion of antigen loading to TAP

Answer 7

EBV’s (EBNAI) cannot be processed by the proteasome
HSV’s (ICP47) blocks access of the processed peptide to TAP
CMV’s (US6) stops ATP binding to TAP preventing translocation

Question 8

Explain how viruses modulate tapasin function and prevent MHC transport

Answer 8

CMV US3 binds tapasin and prevent peptides being loaded to MHC
Adenovirus (E3-19K) prevents recruitment of TAP to tapasin and also retains MHC in the endoplasmic reticulum

Question 9

Explain how viruses interfere with MHC presentation a the cell surface

Answer 9

KSHV (kK3) protein induces polyubiquitinylation and internalization of MHC.
From the internalized endosome, MHC is passed to lysosomes where it is degraded.

Question 10

How do viruses avoid NK killing

Answer 10

Viruses that disrupt MHC presentation would end up being killed by NK cells as they kill cells that do not display MHC
Viruses encode MHC analogues (CMV gpUL40) or upregulate MHC.

Question 11

What causes antigenic variation in viruses

Answer 11

Evolutionary pressure exerted by antibodies drives viruses to change their antigens, antigenic drift e.g. influenza, HIV quasispecies
Introduction of new subtypes from animal source e.g. influenza antigenic shift
Existing as different genetically stable serotypes that cocirculate in humans (antigenic variation) e.g. rhinovirus - 20 serotypes

Question 12

Give an example of antibody-dependent enhancement and state what the consequence of this could be

Answer 12

Dengue
Exists as 4 different serotypes, and antibodies against a previously-contracted one can bind to a different serotype but it doesn’t neutralize it.
This leads to antibody-dependent enhancement of the virus and the classic haemorrhagic fever.

Question 13

What is the function of the TAP protein

Answer 13

load viral peptides onto MHC

Question 14

What is the main viral antigen of influenza

Answer 14

haemagglutinin