Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation
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Peer-reviewed
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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.
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Keywords
cytomegalovirus, human, immune evasion, immunology, infectious disease, microbiology, natural killer cell, virus
Journal Title
eLife
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Journal ISSN
2050-084X
2050-084X
2050-084X
Volume Title
6
Publisher
eLife
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Sponsorship
Medical Research Council (G0901682)
Wellcome Trust (101835/Z/13/Z)
Wellcome Trust (108070/Z/15/Z)
Wellcome Trust (100140/Z/12/Z)
European Research Council (695551)
Wellcome Trust (101835/Z/13/Z)
Wellcome Trust (108070/Z/15/Z)
Wellcome Trust (100140/Z/12/Z)
European Research Council (695551)
This work was supported by funds from the Wellcome Trust WT090323MA and MRC G1000236. MR/L018373/1. This work was also supported by a Wellcome Trust Principal Research Fellowship (WT101835) to PJL and a Wellcome Trust Senior Fellowship (108070/Z/15/Z) to MPW and a strategic award to Cambridge Institute for Medical Research from the Wellcome Trust (100140). JAP was supported by NIH/NIDDK grant K01 DK098285. BV was supported by projects MEYS – NPS I – LO1413 and Czech Science Foundation P206/12/G151. ER was supported by MH CZ-DRO (MMCI, 00209805). CC and JT were supported by grant G0901682 from the MRC and funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 695551), with partial funding from the National Institute of Health Cambridge Biomedical Research Centre.