1. Computational and Systems Biology
  2. Microbiology and Infectious Disease
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A systematic view on Influenza induced host shut-off

  1. Adi Bercovich-Kinori
  2. Julie Tai
  3. Idit Anna Gelbart
  4. Alina Shitrit
  5. Shani Ben-Moshe
  6. Yaron Drori
  7. Shalev Itzkovitz
  8. Michal Mandelboim
  9. Noam Stern-Ginossar  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. Chaim Sheba Medical Center, Ministry of Health, Israel
Research Article
  • Cited 49
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Cite this article as: eLife 2016;5:e18311 doi: 10.7554/eLife.18311

Abstract

Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient translation of viral mRNAs. Here we use RNA-sequencing and ribosome profiling to explore the mechanisms that are being utilized by Influenza A virus (IAV) to induce host shutoff. We show that viral transcripts are not preferentially translated and instead the decline in cellular protein synthesis is mediated by viral takeover on the mRNA pool. Our measurements also uncover strong variability in the levels of cellular transcripts reduction, revealing that short transcripts are less affected by IAV. Interestingly, these mRNAs that are refractory to IAV infection are enriched in cell maintenance processes such as oxidative phosphorylation. Furthermore we show that the continuous oxidative phosphorylation activity is important for viral propagation. Our results advance our understanding of IAV-induced shutoff, and suggest a mechanism that facilitates the translation of genes with important housekeeping functions.

Data availability

The following data sets were generated
    1. Gelbart IA
    2. Stern-Ginossar N
    (2016) A systematic view on Influenza induced host shut-off
    Publicly available at the NCBI Gene Expression Omnibus (accession no. GSE82232).

Article and author information

Author details

  1. Adi Bercovich-Kinori

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Julie Tai

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Idit Anna Gelbart

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Alina Shitrit

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Shani Ben-Moshe

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Yaron Drori

    Central Virology Laboratory, Chaim Sheba Medical Center, Ministry of Health, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Shalev Itzkovitz

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0685-2522
  8. Michal Mandelboim

    Central Virology Laboratory, Chaim Sheba Medical Center, Ministry of Health, Ramat-Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  9. Noam Stern-Ginossar

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    noam.stern-ginossar@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3583-5932

Funding

Human Frontier Science Program

  • Noam Stern-Ginossar

Israel Science Foundation

  • Noam Stern-Ginossar

Israeli Centers for Research Excellence

  • Noam Stern-Ginossar

European Research Council

  • Noam Stern-Ginossar

Marie Curie integration grant

  • Noam Stern-Ginossar

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

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: May 30, 2016
  2. Accepted: August 14, 2016
  3. Accepted Manuscript published: August 15, 2016 (version 1)
  4. Version of Record published: September 19, 2016 (version 2)

Copyright

© 2016, Bercovich-Kinori 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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