title: Selective down-regulation of the NKG2D ligand H60 by mouse cytomegalovirus m155 glycoprotein.
abstract: Both human and mouse cytomegaloviruses (CMVs) encode proteins that inhibit the activation of NK cells by down-regulating cellular ligands for the activating NK cell receptor NKG2D. Up to now, three ligands for the NKG2D receptor, named RAE-1, H60, and MULT-1, have been identified in mice. The resistance of mouse strains to murine CMV (MCMV) infection is determined by their ability to generate an effective NK cell response. The MCMV gene m152, a member of the m145 gene family, down-regulates the expression of RAE-1 in order to avoid NK cell control in vivo. Here we report that the m155 gene, another member of the m145 gene family, encodes a protein that interferes with the expression of H60 on the surfaces of infected cells. Deletion of the m155 gene leads to an only partial restoration of H60 expression on the cell surface, suggesting the involvement of another, so far unknown, viral inhibitor. In spite of this, an m155 deletion mutant virus shows NK cell-dependent attenuation in vivo. The acquisition of endo-beta-N-acetylglucosaminidase H resistance and the preserved half-life of H60 in MCMV-infected cells indicate that the m155-mediated effect must take place in a compartment after H60 exits from the ERGIC-cis-Golgi compartment.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Milena
authors.initials: M
authors.lastname: Hasan
authors.forename: Astrid
authors.initials: A
authors.lastname: Krmpotic
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ruzsics
authors.forename: Ivan
authors.initials: I
authors.lastname: Bubic
authors.forename: Tihana
authors.initials: T
authors.lastname: Lenac
authors.forename: Anne
authors.initials: A
authors.lastname: Halenius
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
mesh_terms: D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation; D017353:Gene Deletion; D005814:Genes, Viral; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism*; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D004279:DNA, Viral; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014764:Viral Proteins; C114735:minor H antigen H60