L25 - Viral evasion of Adaptive response Flashcards
what can host-viral balance range from
host-viral balance is the dynamic interaction between virus and host cell
latent/non-cytopathic = virus persists without causing significant damage to host
- replicates at low levels without killing host
cytopathic = causes damage andf replicates
which role of antibodies is most important for fighting viruses
neutralisation
- binds to spike protein/adhesin
can block attachemt to host cell —> prevent viral proteins binding
or intefere with endocytosis
or even prevent uncoating AFTER endocytosis by stabilising capsid = lysosomes kill pathogen
what can antibodies do to aid phagocytosis
aggregation
= clumping of viral particles
2 key viral evasion strategies to escape antibodies/humoral
- Atigenic variation
- steric inaccessibiltiy of receptor binding site:
- buried sites = bury antigens
- glycan shield = shield antigens
what do RNA viruses have that allow high antigenic variation
RNA polymerases/reverse transcriptase has high error rate
and no proof-reading mechanism
= antigenic shift and quasi species
what is a quasispecies
quasispecies isn’t a single viral genome but a cloud of variants with a “master sequence”
= most common genome in the population
= arises from continous error prone replication and lack of proof-reading mechanisms
what is stuctural plasticity
the ability of a virus to tolerate changes to genome/stuctural proteins
= while maintaining function
where in the viral genome does antigenic variation most occor
Hypervariable regions (HVRs)
= usaully surface proteins
= can produce variants that act as decoys to the normal surface protein = prevent immune response
glycan shield hypothesis with HIV as example
HIV does NOT mutate gp120/gp41 evelope genes = constant regions
= strange as these would produce a large immune response
- constantly changing patterns of glycosylation
- glycans are ‘stolen’ from host cell = viewed as self
- changing which proteins are glycsolated with which sugars evades immune system
= glycosylation is the addition of sugar chains to proteins
role of gp120 and gp41 in HIV - why they need glycan shield
gp120/gp41 = ‘env’ proteins
gp120:
- adhesion to CD4 and interaction with CCR5 chemokine receptor
gp41:
facilitates fusion of viral envelope to cell membrane
= constant regions that dont change would produce suffiecient immune response
evasion of antibody response by SARS-CoV-2
changes in Receptor Binding Domains (RBD)
‘supersite’ for antibodies in N-terminal domain (NTD) of spike protein
= antibodies that bind here are particularly effective
virus causes deletions/mutations in NTD changing shape
describe 2 ways that Viruses escape T-cells/NK cells - cell mediated response
- antigenic variation can produce large epitopes
= region of antigen bound by MHC/TCR
cannot be bound by MHC-1 to be presented
- downregulation of MHC BUT this can increase killing by NK
homologs of MHc produced to trick immune system
how do viruses solve the problem of downregulating MHC molecules which SHOULD increase NK killing
express MHC-1 ‘like’ receptors/homologs
= bind to NK cells as inhibitors ligand
OR inhibition of NK activator ligand
- MICA
name an activating ligand for NK cells
MICA
(MHC Class I-related chain A)
= stress molecule upregulated on infection
simple MHC-1 presentation pathway
- ubiquitinated proteins are targetted for degredation by proteosomes
- peptides enter lumen of ER via TAP
- MHC-1 forms PLC (protein-loading-complex) and binds to peptide
- transported to the surface
how do viruses affect MHC class 1/2 presentation - HIV example
can happen at nearky all the stages by different viruses
- HIV produces Nef protein
- causes internalisation + degredation of MHC molecules on cell surface
= less MHC-1 + MHC-2 on cell surface
describe how HPV interferes with MHC-2 antigen presentation
HPV prevents acidification of early endosomes
- E5 protein prevents H+ being pumped in
- no proteins degraded = no peptides
= nothing to fuse with PLC/MHC-2 complex
what is Human cytomegalovirus (hCMV)
herpesvirus
generally asymptomatic BUT major cause of death in immunocomprimised adults
= targets Nk, CD4 and CD8 T-cells
= not fully cleared from infected cels
produces many proteins that affect MHC presentation
describe teh roke of US2 hCMV gene in MHC modulation
downregulation of MHC-1 + MHC-2
2 key ways of viral avoidance of NK and CD8 cell responses
- disruption of MHC antigen presentation
- upregulation of MHC homologs for NK inhibitory ligand- Ul40 + MICA
= act as inhibitory ligand instead of ‘missing’ MHC
describe the latency mechansim of Epstein-Barr viral (EBV) infections
EBV causes productive/lytic infection in epithelial cells BUT latent infection in B-cells
EBNAs are viral proteins that bind to circular viral genome and maintain it in nucleus
in NON-INTEGRATED state
= no new viral particles = dormant
when in lytic form EBNAs are downregulated = replication
LMPs promote B-cell proliferation
= virus is passed on to daughter cells due to EBNA action
