1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation

  1. Ceri Alan Fielding
  2. Michael P Weekes
  3. Luis V Nobre
  4. Eva Ruckova
  5. Gavin S Wilkie
  6. Joao A Paulo
  7. Chiwen Chang
  8. Nicolás M Suárez
  9. James A Davies
  10. Robin Antrobus
  11. Richard J Stanton
  12. Rebecca J Aicheler
  13. Hester Nichols
  14. Borek Vojtesek
  15. John Trowsdale
  16. Andrew J Davison
  17. Steven P Gygi
  18. Peter Tomasec
  19. Paul J Lehner
  20. Gavin WG Wilkinson  Is a corresponding author
  1. Cardiff University School of Medicine, United Kingdom
  2. Cambridge Institute for Medical Research, United Kingdom
  3. Masaryk Memorial Cancer Institute, Czech Republic
  4. MRC-University of Glasgow Centre for Virus Research, United Kingdom
  5. Harvard Medical School, United States
  6. University of Cambridge, United Kingdom
  7. Cardiff Metropolitan University, United Kingdom
Research Article
  • Cited 28
  • Views 1,895
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Cite this article as: eLife 2017;6:e22206 doi: 10.7554/eLife.22206

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

  1. Ceri Alan Fielding

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5817-3153
  2. Michael P Weekes

    Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Luis V Nobre

    Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Eva Ruckova

    Regional Center for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  5. Gavin S Wilkie

    MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Joao A Paulo

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Chiwen Chang

    Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicolás M Suárez

    MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. James A Davies

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Robin Antrobus

    Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Richard J Stanton

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Rebecca J Aicheler

    Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Hester Nichols

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Borek Vojtesek

    Regional Center for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  15. John Trowsdale

    Immunology Division, Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Andrew J Davison

    MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Steven P Gygi

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Peter Tomasec

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Paul J Lehner

    Cambridge Institute for Medical Research, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9383-1054
  20. Gavin WG Wilkinson

    Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
    For correspondence
    Wilkinsongw1@cardiff.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5623-0126

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)

  • John Trowsdale

European Research Council (695551)

  • John Trowsdale

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.

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.

Reviewing Editor

  1. Wayne M Yokoyama, Howard Hughes Medical Institute, Washington University School of Medicine, United States

Publication history

  1. Received: October 8, 2016
  2. Accepted: February 9, 2017
  3. Accepted Manuscript published: February 10, 2017 (version 1)
  4. Accepted Manuscript updated: February 14, 2017 (version 2)
  5. 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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