Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60.
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.
Arapović
Jurica
J
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
Lenac Rovis
Tihana
T
Reddy
Anil Butchi
AB
Krmpotić
Astrid
A
Jonjić
Stipan
S
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D018146:Muromegalovirus / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D011961:Receptors, Fc / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
D002352:Carrier Proteins; C110265:Fcr-1 protein, Mouse cytomegalovirus 1; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011961:Receptors, Fc; C468260:UL16 binding protein 1, mouse; D014764:Viral Proteins; C104783:m152 protein, cytomegalovirus; C114735:minor H antigen H60