title: Viral interference with B7-1 costimulation: a new role for murine cytomegalovirus fc receptor-1.
abstract: Murine CMV (MCMV), a beta-herpesvirus, infects dendritic cells (DC) and impairs their function. The underlying events are poorly described. In this study, we identify MCMV m138 as the viral gene responsible for promoting the rapid disappearance of the costimulatory molecule B7-1 (CD80) from the cell surface of DC. This was unexpected, as m138 was previously identified as fcr-1, a putative virus-encoded FcR. m138 impaired the ability of DC to activate CD8+ T cells. Biochemical analysis and immunocytochemistry showed that m138 targets B7-1 in the secretory pathway and reroutes it to lysosomal associated membrane glycoprotein-1+ compartments. These results show a novel function for m138 in MCMV infection and identify the first viral protein to target B7-1.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115. USA.
authors.forename: Justine D
authors.initials: JD
authors.lastname: Mintern
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Klemm
authors.forename: Markus
authors.initials: M
authors.lastname: Wagner
authors.forename: Marie Eve
authors.initials: ME
authors.lastname: Paquet
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Napier
authors.forename: You Me
authors.initials: YM
authors.lastname: Kim
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Koszinowski
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology; D006023:Glycoproteins; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus; D021381:Protein Transport; D011961:Receptors, Fc / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D018122:B7-1 Antigen; C110265:Fcr-1 protein, Mouse cytomegalovirus 1; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D014764:Viral Proteins