L21: Viral evasion of adaptive immune response Flashcards
What assists DNA viruses in evading the immune system?
Having a large genome capacity to encode for factors which aid evasion. DNA viruses can also incorporate additional host gene sequences into their genome.
What does the innate cytoplasmic DNA receptor cGAS (cyclic GMP-AMP) to assist immune response.
cGAS protein recognises DNA in the cytoplasm and binds to it to produce cGAMP. cGAMP binds to the adaptor STING on the ER which activates TBK1. This molecule phosphorylates IRF3 and NFkB. End result is IFN and cytokine production.
What prevents RNA viruses from accomodating extra sequences from their host?
Having a small compact genome due to evolutionary constraints.
How do viruses evade antibodies and T cells?
Evasion through latency (such as HSV in neurons and EBV in B cells).
What are the characteristics of latency 1) 2) 3)
1) Viral genome persists intact so virus can be produced at a later time.
2) During latency, expression of viral genes are absent or inefficient
3) Therefore, immune detection is reduced or eliminated
How does HSV, VZV (neurons) and EBV (B cells) become latent?
They infect a non-replicating cell.
How does EBV (B cells) and HIV (T cells) become latent?
Viral genome is replicated in conjunction with host DNA replication.
List the other forms of persistence 1) 2) 3)
1) Chronic infection
2) Non-cytopathic infection of inaccessible site
3) acute wth late complications
Describe the mechanisms of chronic infection with examples 1) 2)
1) Hep B produce decoy virus-like particles of surface antigen so the immune system targets those instead
2) Hep C produce quasispecies through mutation, which causes immune exhaustion
Describe how HPV employs mechanisms of non-cytopathic infection of an inaccessible site and how this allows for persistence.
HPV delays/avoids immune response induction by not making structural proteins in lower skin layers, avoiding immune recognition and clearance.
How does the body develop slow progressing fatal CNS disease from an acute measles infection (SSPE)
The immune response selects for a variant of measles that under-expresses its surface glycoproteins/matrix proteins. The virus no longer can bud but the genome spreads from neuron to neuron.
Describe the process of antigenic variation and how this allows for the body to neutralise antibody and defend against viruses.
Antibodies bind to receptor-binding domains to prevent virus from binding to block endocytosis or uncoating in endosome.
What is antigenic drift and how does it promote viral evasion?
A change in the antigenic structure of the virus. This allows the virus to escape neutralisation by pre-existing antibodies.
How does antigenic drift occur?
RdRp makes errors during replication so spontaneous variation and point mutations occur, some of which are advantageous and lead to escape.
how does antigenic drift occur in influenza?
Occurs on a population scale. Mutation accumulates as the virus spreads between people. The virus cannot mutate too rapidly as all segments need to associate in the particle.
How does antigenic drift occur in HIV?
Diversity arises within a single patient.
explain how a drift in T cell epitopes assists in viral evasion
Mutations can change anchor residues, change flanking amino acids or change the TCR epitope, preventing epitope binding less well to MHC or preventing T cells from recognising peptides.
How do dendritic cells prime T cells?
Immature D cells bind and load antigen onto MHC II and mature and migrate to the LN. They present these antigens to T cells for priming and activation.
Which viruses intercept dendritic cell priming T cell pathway? 1) 2) 3) 4)
1) Vaccinia
2) HSV
3) Vaccinia and HCV
4) Measles and CMV
