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

Kedzierski, L; Tate, MD; Hsu, AC; Kolesnik, TB; Linossi, EM; Dagley, L; Dong, Z; Freeman, S; Infusini, G; Starkey, MR; Bird, NL; Chatfield, SM; Babon, JJ; Huntington, N; Belz, G; Webb, A; Wark, PA; Nicola, NA; Xu, J; Kedzierska, K; Hansbro, PM; Nicholson, SE

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

Kedzierski, L Tate, MD Hsu, AC Kolesnik, TB Linossi, EM Dagley, L Dong, Z Freeman, S Infusini, G Starkey, MR Bird, NL Chatfield, SM Babon, JJ Huntington, N Belz, G Webb, A Wark, PA Nicola, NA Xu, J Kedzierska, K Hansbro, PM

Nicholson, SE

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Publication Type:: Journal Article
Citation:: eLife, 2017, 6
Issue Date:: 2017-02-14

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Field	Value	Language
dc.contributor.author	Kedzierski, L	en_US
dc.contributor.author	Tate, MD	en_US
dc.contributor.author	Hsu, AC	en_US
dc.contributor.author	Kolesnik, TB	en_US
dc.contributor.author	Linossi, EM	en_US
dc.contributor.author	Dagley, L	en_US
dc.contributor.author	Dong, Z	en_US
dc.contributor.author	Freeman, S	en_US
dc.contributor.author	Infusini, G	en_US
dc.contributor.author	Starkey, MR	en_US
dc.contributor.author	Bird, NL	en_US
dc.contributor.author	Chatfield, SM	en_US
dc.contributor.author	Babon, JJ	en_US
dc.contributor.author	Huntington, N	en_US
dc.contributor.author	Belz, G	en_US
dc.contributor.author	Webb, A	en_US
dc.contributor.author	Wark, PA	en_US
dc.contributor.author	Nicola, NA	en_US
dc.contributor.author	Xu, J	en_US
dc.contributor.author	Kedzierska, K	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Nicholson, SE	en_US
dc.date.available	2017-02-06	en_US
dc.date.issued	2017-02-14	en_US
dc.identifier.citation	eLife, 2017, 6	en_US
dc.identifier.uri	http://hdl.handle.net/10453/126211
dc.description.abstract	© Kedzierski et al. 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.	en_US
dc.relation.ispartof	eLife	en_US
dc.relation.isbasedon	10.7554/eLife.20444	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Influenza A virus	en_US
dc.subject.mesh	Orthomyxoviridae Infections	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Body Weight	en_US
dc.subject.mesh	Receptor, Epidermal Growth Factor	en_US
dc.subject.mesh	Cytokines	en_US
dc.subject.mesh	Viral Load	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Suppressor of Cytokine Signaling Proteins	en_US
dc.subject.mesh	ErbB Receptors	en_US
dc.title	Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

© Kedzierski et al. 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.

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http://hdl.handle.net/10453/126211