eLife (Feb 2017)
Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling
- Lukasz Kedzierski,
- Michelle D Tate,
- Alan C Hsu,
- Tatiana B Kolesnik,
- Edmond M Linossi,
- Laura Dagley,
- Zhaoguang Dong,
- Sarah Freeman,
- Giuseppe Infusini,
- Malcolm R Starkey,
- Nicola L Bird,
- Simon M Chatfield,
- Jeffrey J Babon,
- Nicholas Huntington,
- Gabrielle Belz,
- Andrew Webb,
- Peter AB Wark,
- Nicos A Nicola,
- Jianqing Xu,
- Katherine Kedzierska,
- Philip M Hansbro,
- Sandra E Nicholson
Affiliations
- Lukasz Kedzierski
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Michelle D Tate
- ORCiD
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia; Monash University, Clayton, Australia
- Alan C Hsu
- ORCiD
- Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia
- Tatiana B Kolesnik
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Edmond M Linossi
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Laura Dagley
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Zhaoguang Dong
- Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- Sarah Freeman
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Giuseppe Infusini
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Malcolm R Starkey
- Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia
- Nicola L Bird
- Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Australia
- Simon M Chatfield
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Jeffrey J Babon
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Nicholas Huntington
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Gabrielle Belz
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Andrew Webb
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Peter AB Wark
- Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia
- Nicos A Nicola
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- Jianqing Xu
- Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- Katherine Kedzierska
- Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Australia
- Philip M Hansbro
- Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia
- Sandra E Nicholson
- ORCiD
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia
- DOI
- https://doi.org/10.7554/eLife.20444
- Journal volume & issue
-
Vol. 6
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) five 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.
Keywords
