Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
- Cardiff University School of Medicine, United Kingdom
- Cambridge Institute for Medical Research, United Kingdom
- Masaryk Memorial Cancer Institute, Czech Republic
- MRC-University of Glasgow Centre for Virus Research, United Kingdom
- Harvard Medical School, United States
- University of Cambridge, United Kingdom
- Cardiff Metropolitan University, United Kingdom
Abstract
The human cytomegalovirus (HCMV) US12 family consists of ten sequentially arranged genes (US12-21) with poorly characterized function. We now identify novel NK cell evasion functions for four members: US12, US14, US18 and US20. Using a systematic multiplexed proteomics approach to quantify ~1,300 cell surface and ~7,200 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.
Article and author information
Author details
Ceri Alan Fielding
Gavin WG Wilkinson
Funding
Medical Research Council (MRC G1000236,MR/L018373/1)
- Peter Tomasec
- Gavin WG Wilkinson
European Research Council (695551)
- John Trowsdale
Wellcome (WT090323MA)
- Peter Tomasec
- Gavin WG Wilkinson
Wellcome (WT101835)
- Paul J Lehner
Wellcome (108070/Z/15/Z)
- Michael P Weekes
NIH/NIDDK (K01 DK098285)
- Joao A Paulo
Czech Science Foundation (P206/12/G151)
- Borek Vojtesek
Medical Research Council (G0901682)
- Chiwen Chang
European Research Council (695551)
- Chiwen Chang
Wellcome (100140)
- Paul J Lehner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wayne M Yokoyama, Howard Hughes Medical Institute, Washington University School of Medicine, United States
Ethics
Human subjects: Healthy adult volunteers provided blood for this study following written informed consent (approved by the Cardiff University School of Medicine Ethics Committee Ref. no: 10/20) or buffy coats provided by the Welsh Blood Service, following informed consent.
Version history
- Received: October 8, 2016
- Accepted: February 9, 2017
- Accepted Manuscript published: February 10, 2017 (version 1)
- Accepted Manuscript updated: February 14, 2017 (version 2)
- Version of Record published: March 27, 2017 (version 3)
Copyright
© 2017, Fielding et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
eLife 6:e22206.
https://doi.org/10.7554/eLife.22206
Further reading
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