Herpes simplex virus infection downmodulates NKG2D ligand expression

Scand J Immunol. 2009 May;69(5):429-36. doi: 10.1111/j.1365-3083.2009.02241.x. Epub 2009 Feb 26.


Herpes simplex virus (HSV) type 1 infection may cause orofacial infections in humans. The virus resides in a latent form in neural ganglia and occasionally reactivates and infects epithelial cells. Natural killer (NK) cells have been implicated in immune control of herpes virus infections, possibly by downmodulating major histocompatibility complex (MHC) class I and by other, as yet unidentified, mechanisms. Upon HSV-1 infection of cell lines, surface levels of NKG2D ligands MHC class I related proteins (MIC) A and UL16 binding protein 2 were downmodulated due to late viral gene product(s). As also MHC class I levels were reduced by HSV-1, NK cell recognition of HeLa cells was not affected by infection. Total cellular MICA contents remained unchanged, suggesting masking, internalization or intracellular retention of MICA as possible mechanisms of viral downregualtion of MICA surface levels. Furthermore, NK cells from patients with active HSV-1 infection had a tendency towards increased expression level of the activating receptor NKG2D. These data support a role for NKG2D-MICA interactions in immune responses to HSV-1 reactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Line, Tumor
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins
  • Gene Expression / drug effects
  • HeLa Cells
  • Herpes Simplex / blood
  • Herpes Simplex / immunology
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / immunology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immediate-Early Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interleukin-15 / pharmacology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / virology
  • Ligands
  • Male
  • Middle Aged
  • Mutation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ubiquitin-Protein Ligases / genetics
  • Young Adult


  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-15
  • Ligands
  • MHC class I-related chain A
  • ULBP2 protein, human
  • Ubiquitin-Protein Ligases
  • Vmw110 protein, Human herpesvirus 1