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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Modulation of natural killer cells by human cytomegalovirus

Gavin W G Wilkinson1, Peter Tomasec, Richard J Stanton

  • 1Department of Medical Microbiology, Cardiff University, Tenovus Building, Heath Park, Cardiff CF14 4XX, UK. WilkinsonGW1@cardiff.ac.uk

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology
|December 11, 2007
PubMed

Insights

Human cytomegalovirus (HCMV) evades natural killer (NK) cells by downregulating activating ligands and upregulating inhibitory signals. This immune evasion is crucial for persistent HCMV infections.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Human cytomegalovirus (HCMV) establishes lifelong infections, constantly challenged by the immune system.
  • HCMV-infected cells resist natural killer (NK) cell killing through sophisticated immune evasion strategies.
  • Understanding HCMV's immune evasion mechanisms is key to comprehending NK cell function.

Purpose of the Study:

  • To identify and characterize the viral factors and mechanisms HCMV employs to avoid NK cell recognition and lysis.
  • To elucidate how HCMV modulates the expression of ligands for NK cell receptors, particularly NKG2D and those affected by MHC-I downregulation.
  • To investigate HCMV's strategies for counteracting the effects of cell-cell junction disruption on NK cell activation.

Main Methods:

  • Analysis of viral gene products (proteins and microRNA) involved in NK cell immune evasion.
  • Investigating the regulation of NK cell receptor ligands (e.g., NKG2D ligands, HLA-E, CD155) during HCMV infection.
  • Studying the impact of viral proteins like UL16, UL18, UL40, UL83, UL141, UL142, and miR-UL112 on cellular and viral immune interactions.

Main Results:

  • Six HCMV proteins (UL16, UL18, UL40, UL83, UL141, UL142) and miR-UL112 suppress NK cell recognition.
  • HCMV utilizes UL16, UL142, and miR-UL112 to suppress NKG2D ligand presentation.
  • HCMV modulates MHC-I expression via UL18 and upregulates HLA-E using UL40, while UL141 suppresses CD155 surface expression.

Conclusions:

  • HCMV employs multiple viral factors to systematically evade NK cell detection and lysis.
  • These mechanisms involve downregulating activating ligands and manipulating MHC-I related pathways.
  • HCMV's modulation of NK cell recognition provides critical insights into NK cell biology and viral immune escape.

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