1. Microbiology and Infectious Disease
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Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation

  1. Myra Hosmillo
  2. Jia Lu
  3. Michael R McAllaster
  4. James B Eaglesham
  5. Xinjie Wang
  6. Edward Emmott
  7. Patricia Domingues
  8. Yasmin Chaudhry
  9. Tim J Fitzmaurice
  10. Matthew KH Tung
  11. Marc Dominik Panas
  12. Gerald McInerney
  13. Nicolas Locker
  14. Craig B Wilen  Is a corresponding author
  15. Ian G Goodfellow  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. Washington University School of Medicine, United States
  3. Karolinska Institutet, Sweden
  4. University of Surrey, United Kingdom
  5. Yale School of Medicine, United States
Research Article
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Cite this article as: eLife 2019;8:e46681 doi: 10.7554/eLife.46681

Abstract

Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across the Norovirus genus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating ribosome recruitment. Our data uncovers a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifies the first host factor with pan-norovirus pro-viral activity.

Data availability

VPg proteomics raw data, search results and FASTA files can be found as part of PRIDE submission PXD007585. Flag-virus proteomics raw data, search results and FASTA files can be found as part of PRIDE submission PXD011779.

The following data sets were generated

Article and author information

Author details

  1. Myra Hosmillo

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3514-7681
  2. Jia Lu

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael R McAllaster

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. James B Eaglesham

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Xinjie Wang

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Edward Emmott

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Patricia Domingues

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Yasmin Chaudhry

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Tim J Fitzmaurice

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1403-2495
  10. Matthew KH Tung

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Marc Dominik Panas

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7373-0341
  12. Gerald McInerney

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  13. Nicolas Locker

    School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Craig B Wilen

    Department of Laboratory Medicine and Immunobiology, Yale School of Medicine, New Haven, United States
    For correspondence
    craig.wilen@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
  15. Ian G Goodfellow

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    ig299@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9483-510X

Funding

Wellcome (207498/Z/17/Z)

  • Myra Hosmillo
  • Jia Lu
  • James B Eaglesham
  • Xinjie Wang
  • Edward Emmott
  • Patricia Domingues
  • Yasmin Chaudhry
  • Tim J Fitzmaurice
  • Matthew KH Tung
  • Ian G Goodfellow

National Institutes of Health (AI128043)

  • Craig B Wilen

Biotechnology and Biological Sciences Research Council (BB/N001176/1)

  • Jia Lu
  • Ian G Goodfellow

Wellcome (104914/Z/14/Z)

  • Ian G Goodfellow

Burroughs Wellcome Fund

  • Craig B Wilen

Churchill College, University of Cambridge

  • James B Eaglesham

Biotechnology and Biological Sciences Research Council (BB/000943N/1)

  • Nicolas Locker

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

Reviewing Editor

  1. Karla Kirkegaard, Stanford University School of Medicine, United States

Publication history

  1. Received: March 8, 2019
  2. Accepted: August 9, 2019
  3. Accepted Manuscript published: August 12, 2019 (version 1)
  4. Version of Record published: September 11, 2019 (version 2)

Copyright

© 2019, Hosmillo 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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Further reading

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