1. Chromosomes and Gene Expression
  2. Microbiology and Infectious Disease
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IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP

  1. Arunava Roy  Is a corresponding author
  2. Anandita Ghosh
  3. Binod Kumar
  4. Bala Chandran  Is a corresponding author
  1. University of South Florida, United States
  2. Rosalind Franklin University of Medicine and Science, United States
Research Article
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Cite this article as: eLife 2019;8:e49500 doi: 10.7554/eLife.49500

Abstract

IFI16, an innate immune DNA sensor, recognizes the nuclear episomal herpes viral genomes and induces the inflammasome and interferon-β responses. IFI16 also regulates cellular transcription and act as a DNA virus restriction factor. IFI16 knockdown disrupted the latency of Kaposi's sarcoma associated herpesvirus (KSHV) and induced lytic transcripts. However, the mechanism of IFI16's transcription regulation is unknown. Here, we show that IFI16 is in complex with the H3K9 methyltransferase SUV39H1 and GLP and recruits them to the KSHV genome during de novo infection and latency. The resulting depositions of H3K9me2/me3 serve as a docking site for the heterochromatin inducing HP1α protein leading into the IFI16 dependent epigenetic modifications and silencing of KSHV lytic genes. These studies suggest that IFI16's interaction with H3K9MTases is one of the potential mechanisms by which IFI16 regulates transcription and establish an important paradigm of an innate immune sensor's involvement in epigenetic silencing of foreign DNA.

Article and author information

Author details

  1. Arunava Roy

    Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United States
    For correspondence
    arunava@health.usf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8486-0539
  2. Anandita Ghosh

    Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Binod Kumar

    Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bala Chandran

    Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United States
    For correspondence
    chandran@health.usf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5319-8714

Funding

Public Health Institute (CA 180758)

  • Bala Chandran

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

Reviewing Editor

  1. Sara L Sawyer, University of Colorado Boulder, United States

Publication history

  1. Received: June 19, 2019
  2. Accepted: November 1, 2019
  3. Accepted Manuscript published: November 4, 2019 (version 1)

Copyright

© 2019, Roy 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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