A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression
- University of California, Berkeley, United States
- University of California, San Francisco, United States
- Oregon Health and Science University, United States
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.
Article and author information
Author details
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
- 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
- Received: January 27, 2016
- Accepted: November 7, 2016
- Accepted Manuscript published: November 22, 2016 (version 1)
- 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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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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