Suppressor of Cytokine Signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling
- The Walter and Eliza Hall Institute of Medical Research, Australia
- Hudson Institute of Medical Research, Australia
- The University of Newcastle, Australia
- Fudan University, China
- University of Melbourne, Australia
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
Sandra E Nicholson
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.
Reviewing Editor
- Masato Kubo, RIKEN, Japan
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).
Version history
- Received: August 8, 2016
- Accepted: February 6, 2017
- Accepted Manuscript published: February 14, 2017 (version 1)
- 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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Suppressor of Cytokine Signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling
eLife 6:e20444.
https://doi.org/10.7554/eLife.20444
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