Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling

Lukasz Kedzierski, Michelle 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 KedzierskaPhilip M Hansbro, Sandra E Nicholson

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33 Citations (Scopus)

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.

Original languageEnglish
Article numbere20444
Number of pages27
JournaleLife
Volume6
DOIs
Publication statusPublished - 14 Feb 2017

Keywords

  • Influenza
  • COPD
  • SOCS5
  • EGFR
  • P13K
  • innate immunity

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