title: NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145.
abstract: The NK cell-activating receptor NKG2D interacts with three different cellular ligands, all of which are regulated by mouse cytomegalovirus (MCMV). We set out to define the viral gene product regulating murine UL16-binding protein-like transcript (MULT)-1, a newly described NKG2D ligand. We show that MCMV infection strongly induces MULT-1 gene expression, but surface expression of this glycoprotein is nevertheless completely abolished by the virus. Screening a panel of MCMV deletion mutants defined the gene m145 as the viral regulator of MULT-1. The MCMV m145-encoded glycoprotein turned out to be necessary and sufficient to regulate MULT-1 by preventing plasma membrane residence of MULT-1. The importance of MULT-1 in NK cell regulation in vivo was confirmed by the attenuating effect of the m145 deletion that was lifted after NK cell depletion. Our findings underline the significance of escaping MULT-1/NKG2D signaling for viral survival and maintenance.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Astrid
authors.initials: A
authors.lastname: Krmpotic
authors.forename: Milena
authors.initials: M
authors.lastname: Hasan
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.forename: Tanja
authors.initials: T
authors.lastname: Saulig
authors.forename: Anne
authors.initials: A
authors.lastname: Halenius
authors.forename: Tihana
authors.initials: T
authors.lastname: Lenac
authors.forename: Bojan
authors.initials: B
authors.lastname: Polic
authors.forename: Ivan
authors.initials: I
authors.lastname: Bubic
authors.forename: Anja
authors.initials: A
authors.lastname: Kriegeskorte
authors.forename: Ester
authors.initials: E
authors.lastname: Pernjak-Pugel
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003587:Cytomegalovirus / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D020539:Sequence Analysis, Protein; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C468260:UL16 binding protein 1, mouse; D014764:Viral Proteins