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

• Published in: eLife Vol. 6
• Main Authors: Kedzierski, Lukasz, Tate, Michelle D, Hsu, Alan C, Kolesnik, Tatiana B, Linossi, Edmond M, Dagley, Laura, Dong, Zhaoguang, Freeman, Sarah, Infusini, Giuseppe, Starkey, Malcolm R, Bird, Nicola L, Chatfield, Simon M, Babon, Jeffrey J, Huntington, Nicholas, Belz, Gabrielle, Webb, Andrew, Wark, Peter Ab, Nicola, Nicos A, Xu, Jianqing, Kedzierska, Katherine, Hansbro, Philip M, Nicholson, Sandra E
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 14-02-2017; eLife Sciences Publications, Ltd
• Subjects: Animals; Body Weight; Cell Biology; Chronic obstructive pulmonary disease; COPD; Cytokines - secretion; Disease Models, Animal; EGFR; Epidermal growth factor; Epidermal growth factor receptors; Epithelial cells; Epithelium; Humans; Inflammation; influenza; Influenza A; Influenza A virus - immunology; innate immunity; Kinases; Mice; Mice, Knockout; Microbiology and Infectious Disease; Mortality; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; PI3K; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Respiratory tract; Signal Transduction; SOCS5; Suppressor of Cytokine Signaling Proteins - deficiency; Suppressor of Cytokine Signaling Proteins - metabolism; Viral infections; Viral Load; influenza; mouse; cell biology; PI3K; innate immunity; infectious disease; microbiology; human; virus; EGFR; COPD; SOCS5
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.20444

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).
-deficient mice exhibit heightened disease severity, with increased viral titres and weight loss.
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.