Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation

• DOI: 10.7554/elife.22206
• Publication Date: 2017-02-10T13:00:15Z
• Authors: Ceri A Fielding; Michael P Weekes; Luis V Nobre; Eva Ruckova; Gavin S Wilkie; Joao A Paulo; Chiwen Chang; Nicolás M Suárez; James A Davies; Robin Antrobus; Richard J Stanton; Rebecca J Aicheler; Hester Nichols; Borek Vojtesek; John Trowsdale; Andrew J Davison; Steven P Gygi; Peter Tomasec; Paul J Lehner; Gavin W G Wilkinson
• Keywords: Proteomics; QH301-705.5; Science; infectious disease; Immunology; 610; Cytomegalovirus; virus; immunology; Viral Proteins; 03 medical and health sciences; 0302 clinical medicine; Humans; Immunologic Factors; human; Biology (General); QH426; cytomegalovirus; Immune Evasion; immune evasion; Q; microbiology; R; Membrane Proteins; natural killer cell; Virus; 3. Good health; Killer Cells, Natural; Host-Pathogen Interactions; Medicine

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.