title: The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60.
abstract: Members of the alpha- and beta-subfamily of herpesviridae encode glycoproteins that specifically bind to the Fc part of immunoglobulin (Ig)G. Plasma membrane resident herpesviral Fc receptors seem to prevent virus-specific IgG from activating antibody-dependent effector functions. We show that the mouse cytomegalovirus (MCMV) molecule fcr-1 promotes a rapid down-regulation of NKG2D ligands murine UL16-binding protein like transcript (MULT)-1 and H60 from the cell surface. Deletion of the m138/fcr-1 gene from the MCMV genome attenuates viral replication to natural killer (NK) cell response in an NKG2D-dependent manner in vivo. A distinct N-terminal module within the fcr-1 ectodomain in conjunction with the fcr-1 transmembrane domain was required to dispose MULT-1 to degradation in lysosomes. In contrast, down-modulation of H60 required the complete fcr-1 ectodomain, implying independent modes of fcr-1 interaction with the NKG2D ligands. The results establish a novel viral strategy for down-modulating NK cell responses and highlight the impressive diversity of Fc receptor functions.
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
authors.forename: Tihana
authors.initials: T
authors.lastname: Lenac
authors.forename: Matthias
authors.initials: M
authors.lastname: Budt
authors.forename: Jurica
authors.initials: J
authors.lastname: Arapovic
authors.forename: Milena
authors.initials: M
authors.lastname: Hasan
authors.forename: Albert
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Simic
authors.forename: Astrid
authors.initials: A
authors.lastname: Krmpotic
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ruzsics
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism*; D018146:Muromegalovirus / Q000378:metabolism* / Q000502:physiology; D041681:NIH 3T3 Cells; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C110265:Fcr-1 protein, Mouse cytomegalovirus 1; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C468260:UL16 binding protein 1, mouse; D014764:Viral Proteins; C114735:minor H antigen H60