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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

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.

Original languageEnglish
Article numbere22206
JournaleLife
Volume6
DOIs
Publication statusPublished - 10 Feb 2017

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