title: Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation.
abstract: The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel natural killer (NK) cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1300 cell surface and ~7200 whole cell proteins, we demonstrate that the US12 family selectively targets plasma membrane proteins and plays key roles in regulating NK ligands, adhesion molecules and cytokine receptors. US18 and US20 work in concert to suppress cell surface expression of the critical NKp30 ligand B7-H6 thus inhibiting NK cell activation. The US12 family is therefore identified as a major new hub of immune regulation.
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Ceri A
authors.identifier: 0000-0002-5817-3153
authors.initials: CA
authors.lastname: Fielding
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.|Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Michael P
authors.identifier: 0000-0003-3196-5545
authors.initials: MP
authors.lastname: Weekes
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Luis V
authors.identifier: 0000-0003-0467-8989
authors.initials: LV
authors.lastname: Nobre
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Ruckova
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Wilkie
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Joao A
authors.identifier: 0000-0002-4291-413X
authors.initials: JA
authors.lastname: Paulo
authors.affiliation: Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Chiwen
authors.initials: C
authors.lastname: Chang
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Nicolás M
authors.identifier: 0000-0001-8429-8374
authors.initials: NM
authors.lastname: Suárez
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Davies
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Robin
authors.identifier: 0000-0001-8608-4011
authors.initials: R
authors.lastname: Antrobus
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Richard J
authors.identifier: 0000-0002-6799-1182
authors.initials: RJ
authors.lastname: Stanton
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Aicheler
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Hester
authors.identifier: 0000-0002-6814-4364
authors.initials: H
authors.lastname: Nichols
authors.affiliation: Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Borek
authors.initials: B
authors.lastname: Vojtesek
authors.affiliation: Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: John
authors.identifier: 0000-0002-0150-5698
authors.initials: J
authors.lastname: Trowsdale
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Andrew J
authors.identifier: 0000-0002-4991-9128
authors.initials: AJ
authors.lastname: Davison
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Peter
authors.identifier: 0000-0002-6745-6198
authors.initials: P
authors.lastname: Tomasec
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Paul J
authors.identifier: 0000-0001-9383-1054
authors.initials: PJ
authors.lastname: Lehner
authors.affiliation: Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Gavin W G
authors.identifier: 0000-0002-5623-0126
authors.initials: GW
authors.lastname: Wilkinson
mesh_terms: D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007155:Immunologic Factors / Q000037:antagonists & inhibitors*; D007694:Killer Cells, Natural / Q000276:immunology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D040901:Proteomics; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D007155:Immunologic Factors; D008565:Membrane Proteins; D014764:Viral Proteins
keywords: cytomegalovirus; human; immune evasion; immunology; infectious disease; microbiology; natural killer cell; virus