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Human Cytomegalovirus Immune Evasion

Human Cytomegalovirus

  • known for variety of immune evasion techniques
  • congenital infection
  • infect many cells: especially respiratory system
  • difficult to create vaccine or use immunotherapy

HCMV

Adaptive Immune Response to Viruses

  • CD8 T cells
  • CD4 T cells
  • B cells
  • Antibodies

Adaptive Immune Evasion Techniques

MHC presentation

  • usually MHC class 1 on every nucleated cell
  • Stop MHC class 1 from going to the ER where it is loaded with a peptide

MHC presentation

Latency

  • enter non replicative state
  • production of IL-10

Latency

Polymorphic

T cells produced to one antigen may not be the same for other strains

Polymorphic

Innate Immune Response

  • NK cells
  • type one interferons
  • other cytokines
  • phagocytes
  • use of PRRs

Innate

Immune Evasion Techniques

STING Pathway Inhibition

  • blocks production of type 1 interferons
  • cannot enter anti viral state

STING

NK cells inhibited

  • NK cells with many activators/ inhibitors
  • without MHC class 1 on a cell, NK not inhibited
  • so HCMV produces 'fake' MHC

NK cells

NK cell inhibition example

  • activating receptor NKp30 binds to B7-H6 on infected cells
  • HCMV with US18 and US20 genes
  • downregulate B7-H6 so that NK cells are not acitvated

NK inhibition mechanism

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