1. Immunology and Inflammation
  2. Microbiology and Infectious Disease

A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression

  1. Trever T Greene
  2. Maria Tokuyama
  3. Giselle M Knudsen
  4. Michele Kunz
  5. James Lin
  6. Alexander L Greninger
  7. Victor R DeFilippis
  8. Joseph L DeRisi
  9. David H Raulet
  10. Laurent Coscoy  Is a corresponding author
  1. University of California, Berkeley, United States
  2. University of California, San Francisco, United States
  3. Oregon Health and Science University, United States
https://doi.org/10.7554/eLife.14749
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Cite this article
  1. Trever T Greene
  2. Maria Tokuyama
  3. Giselle M Knudsen
  4. Michele Kunz
  5. James Lin
  6. Alexander L Greninger
  7. Victor R DeFilippis
  8. Joseph L DeRisi
  9. David H Raulet
  10. Laurent Coscoy
(2016)
A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression
eLife 5:e14749.
https://doi.org/10.7554/eLife.14749
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  3. Download .RIS

Abstract

Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands. We demonstrate that RAE-1 is transcriptionally repressed by histone deacetylase inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by directly interacting with Casein Kinase II and preventing it from activating HDAC3. Accordingly, we found that HDAC inhibiting proteins from human herpesviruses induce human NKG2D ligand ULBP-1. Thus our findings indicate that virally mediated HDAC inhibition can act as a signal for the host to activate NK-cell recognition.

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Author details

  1. Trever T Greene

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Maria Tokuyama

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Giselle M Knudsen

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Michele Kunz

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. James Lin

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Alexander L Greninger

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Victor R DeFilippis

    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Joseph L DeRisi

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. David H Raulet

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Laurent Coscoy

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    lcoscoy@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7337-2345

Funding

National Institutes of Health (R01 AI113041.)

  • David H Raulet

National Institutes of Health (AI 100829)

  • Trever T Greene

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

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

Ethics

Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of California Berkeley. The specific animal use protocol (AUP#R292-0517BCR) was approved by the animal care and use committee (ACUC) of the University of California Berkeley. Every effort was made to minimize suffering.

Version history

  1. Received: January 27, 2016
  2. Accepted: November 7, 2016
  3. Accepted Manuscript published: November 22, 2016 (version 1)
  4. Version of Record published: December 1, 2016 (version 2)

Copyright

© 2016, Greene 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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  1. Trever T Greene
  2. Maria Tokuyama
  3. Giselle M Knudsen
  4. Michele Kunz
  5. James Lin
  6. Alexander L Greninger
  7. Victor R DeFilippis
  8. Joseph L DeRisi
  9. David H Raulet
  10. Laurent Coscoy
(2016)
A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression
eLife 5:e14749.
https://doi.org/10.7554/eLife.14749

Share this article

https://doi.org/10.7554/eLife.14749

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