Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60

Mol Immunol. 2009 Nov;47(1):114-22. doi: 10.1016/j.molimm.2009.02.010. Epub 2009 Mar 17.

Abstract

Both human and mouse cytomegalovirus (CMV) encode proteins that inhibit the activation of NK cells by down-regulating the cellular ligands for activating NK cell receptor, NKG2D. MCMV proteins m145, m152 and m155 interfere with the expression of all known NKG2D ligands, MULT-1, RAE-1 family members and H60, respectively, whereas m138 affects the expression of MULT-1 and H60. Here we show that m152 affects the maturation of newly synthesized RAE-1 molecules, but is not sufficient to prevent surface expression of RAE-1varepsilon. We have identified m138 as a main inhibitor of the surface expression of RAE-1varepsilon. In contrast to m152, m138 affects the surface-resident protein leading to its endocytosis, which can be prevented by a dynamin inhibitor. Moreover, we demonstrated that m138 does not need other viral proteins to down-modulate the expression of RAE-1varepsilon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / genetics
  • Ligands
  • Membrane Glycoproteins / physiology*
  • Membrane Proteins
  • Mice
  • Minor Histocompatibility Antigens / genetics
  • Muromegalovirus / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K / immunology*
  • Receptors, Fc / physiology*
  • Viral Proteins / physiology*

Substances

  • Carrier Proteins
  • Fcr-1 protein, Mouse cytomegalovirus 1
  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • Ligands
  • Membrane Glycoproteins
  • Membrane Proteins
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Fc
  • UL16 binding protein 1, mouse
  • Viral Proteins
  • m152 protein, cytomegalovirus
  • minor H antigen H60