title: Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112.
abstract: Human cytomegalovirus (HCMV) UL141 induces protection against natural killer cell-mediated cytolysis by downregulating cell surface expression of CD155 (nectin-like molecule 5; poliovirus receptor), a ligand for the activating receptor DNAM-1 (CD226). However, DNAM-1 is also recognized to bind a second ligand, CD112 (nectin-2). We now show that HCMV targets CD112 for proteasome-mediated degradation by 48 h post-infection, thus removing both activating ligands for DNAM-1 from the cell surface during productive infection. Significantly, cell surface expression of both CD112 and CD155 was restored when UL141 was deleted from the HCMV genome. While gpUL141 alone is sufficient to mediate retention of CD155 in the endoplasmic reticulum, UL141 requires assistance from additional HCMV-encoded functions to suppress expression of CD112.
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Virginie
authors.initials: V
authors.lastname: Prod'homme
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sugrue
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stanton
authors.affiliation: Department of Microbiology, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Nomoto
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: James
authors.initials: J
authors.lastname: Davies
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Carole R
authors.initials: CR
authors.lastname: Rickards
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cochrane
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Melanie
authors.initials: M
authors.lastname: Moore
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Gavin W G
authors.initials: GWG
authors.lastname: Wilkinson
authors.affiliation: Department of Infection, Immunity and Biochemistry, Section of Medical Microbiology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Tomasec
mesh_terms: D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D017353:Gene Deletion; D006801:Humans; D007108:Immune Tolerance; D053646:Interleukin-2 Receptor beta Subunit / Q000037:antagonists & inhibitors*; D007694:Killer Cells, Natural / Q000276:immunology*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D037521:Virulence Factors / Q000276:immunology / Q000502:physiology*
chemical_list: C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D011991:Receptors, Virus; D014764:Viral Proteins; D037521:Virulence Factors; C066100:poliovirus receptor
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