Control of immune ligands by members ofa cytomegalovirus gene expansionsuppresses natural killer cell activation
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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.
Immunology and Inflammation Microbiology and Infectios Disease;
This article was published open access in Immunology and Inflammation Microbiology and Infectios Disease/eLife on 10 February 2017, available at https://doi.org/10.7554/eLife.22206