1. Cell Biology
  2. Microbiology and Infectious Disease
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Suppressor of Cytokine Signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling

  1. Lukasz Kedzierski
  2. Michelle D Tate
  3. Alan C Hsu
  4. Tatiana B Kolesnik
  5. Edmond M Linossi
  6. Laura Dagley
  7. Zhaoguang Dong
  8. Sarah Freeman
  9. Giuseppe Infusini
  10. Malcolm R Starkey
  11. Nicola L Bird
  12. Simon M Chatfield
  13. Jeffrey J Babon
  14. Nicholas Huntington
  15. Gabrielle Belz
  16. Andrew Webb
  17. Peter AB Wark
  18. Nicos A Nicola
  19. Jianqing Xu
  20. Katherine Kedzierska
  21. Philip M Hansbro  Is a corresponding author
  22. Sandra E Nicholson  Is a corresponding author
  1. The Walter and Eliza Hall Institute of Medical Research, Australia
  2. Hudson Institute of Medical Research, Australia
  3. The University of Newcastle, Australia
  4. Fudan University, China
  5. University of Melbourne, Australia
Research Article
  • Cited 34
  • Views 2,043
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Cite this article as: eLife 2017;6:e20444 doi: 10.7554/eLife.20444

Abstract

Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) 5 has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.

Article and author information

Author details

  1. Lukasz Kedzierski

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Michelle D Tate

    Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0587-5514
  3. Alan C Hsu

    Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Newcastle, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6640-0846
  4. Tatiana B Kolesnik

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Edmond M Linossi

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Laura Dagley

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Zhaoguang Dong

    Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Sarah Freeman

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Giuseppe Infusini

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Malcolm R Starkey

    Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Newcastle, Australia
    Competing interests
    The authors declare that no competing interests exist.
  11. Nicola L Bird

    Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  12. Simon M Chatfield

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  13. Jeffrey J Babon

    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Nicholas Huntington

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Gabrielle Belz

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  16. Andrew Webb

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. Peter AB Wark

    Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Newcastle, Australia
    Competing interests
    The authors declare that no competing interests exist.
  18. Nicos A Nicola

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  19. Jianqing Xu

    Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  20. Katherine Kedzierska

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  21. Philip M Hansbro

    Priority Research Centre for Asthma and Respiratory Diseases, The University of Newcastle, Newcastle, Australia
    For correspondence
    philip.hansbro@newcastle.edu.au
    Competing interests
    The authors declare that no competing interests exist.
  22. Sandra E Nicholson

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
    For correspondence
    snicholson@wehi.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1314-2134

Funding

National Health and Medical Research Council (Project grants #1047248,1045762,Program grant #1016647)

  • Nicos A Nicola
  • Philip M Hansbro
  • Sandra E Nicholson

Victorian State Government, Australia (Operational Infrastructure Scheme grant)

  • Lukasz Kedzierski
  • Tatiana B Kolesnik
  • Edmond M Linossi
  • Laura Dagley
  • Sarah Freeman
  • Simon M Chatfield
  • Nicholas Huntington
  • Gabrielle Belz
  • Andrew Webb
  • Nicos A Nicola
  • Sandra E Nicholson

Australian Research Council (Future Fellowship)

  • Gabrielle Belz

Australian Federal Government (Australian Postgraduate Award)

  • Edmond M Linossi

National Health and Medical Research Council (Fellowship)

  • Michelle D Tate
  • Nicos A Nicola
  • Katherine Kedzierska
  • Philip M Hansbro

National Health and Medical Research Council (IRIISS grant 361646)

  • Lukasz Kedzierski
  • Tatiana B Kolesnik
  • Edmond M Linossi
  • Laura Dagley
  • Sarah Freeman
  • Giuseppe Infusini
  • Simon M Chatfield
  • Nicholas Huntington
  • Gabrielle Belz
  • Andrew Webb
  • Nicos A Nicola
  • Sandra E Nicholson

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

Ethics

Animal experimentation: Animal experiments followed the NHMRC Code of Practice for the Care and Use of Animals for Scientific Purposes guidelines and were approved by the Walter and Eliza Hall Institute's Animal Ethics Committee (Ethics Number: 2014.029).

Human subjects: All subjects gave written informed consent and all procedures were performed according to approval from the University of Newcastle Human Ethics Committee (Ethics Number: H-163-1205).

Reviewing Editor

  1. Masato Kubo, RIKEN, Japan

Publication history

  1. Received: August 8, 2016
  2. Accepted: February 6, 2017
  3. Accepted Manuscript published: February 14, 2017 (version 1)
  4. Version of Record published: March 16, 2017 (version 2)

Copyright

© 2017, Kedzierski 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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