Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus

J Virol. 2009 Aug;83(16):8198-207. doi: 10.1128/JVI.02549-08. Epub 2009 Jun 3.


The NKG2D receptor is one of the most potent activating natural killer cell receptors involved in antiviral responses. The mouse NKG2D ligands MULT-1, RAE-1, and H60 are regulated by murine cytomegalovirus (MCMV) proteins m145, m152, and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60. We show here that one of five RAE-1 isoforms, RAE-1delta, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1delta and RAE-1gamma in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1delta form which remains expressed on the surfaces of infected cells. This differential susceptibility to downregulation by MCMV is not a consequence of faster maturation of RAE-1delta compared to RAE-1gamma but rather an intrinsic property of the mature surface-resident protein. This difference can be attributed to the absence of a PLWY motif from RAE-1delta. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Down-Regulation*
  • Gene Expression
  • Herpesviridae Infections / genetics*
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Killer Cells, Natural / immunology
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Muromegalovirus / genetics
  • Muromegalovirus / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Sequence Homology, Amino Acid
  • Viral Proteins / genetics
  • Viral Proteins / immunology


  • Klrk1 protein, mouse
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Protein Isoforms
  • Raet1c protein, mouse
  • Raet1d, protein, mouse
  • Viral Proteins