title: Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.
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.Socs5levels 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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kedzierski
authors.affiliation: Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia.|Monash University, Clayton, Australia.
authors.forename: Michelle D
authors.identifier: 0000-0002-0587-5514
authors.initials: MD
authors.lastname: Tate
authors.affiliation: Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia.
authors.forename: Alan C
authors.identifier: 0000-0002-6640-0846
authors.initials: AC
authors.lastname: Hsu
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Tatiana B
authors.initials: TB
authors.lastname: Kolesnik
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Edmond M
authors.initials: EM
authors.lastname: Linossi
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Dagley
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Zhaoguang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Freeman
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Infusini
authors.affiliation: Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Starkey
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Australia.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Bird
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Chatfield
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Babon
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Huntington
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Belz
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Webb
authors.affiliation: Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia.
authors.forename: Peter Ab
authors.initials: PA
authors.lastname: Wark
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Nicola
authors.affiliation: Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.affiliation: Priority Research Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute and The University of Newcastle, Newcastle, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Australia.
authors.forename: Sandra E
authors.identifier: 0000-0002-1314-2134
authors.initials: SE
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency / Q000378:metabolism*; D019562:Viral Load
chemical_list: D016207:Cytokines; C408990:SOCS5 protein, human; C485811:Socs5 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; C512478:EGFR protein, human; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: COPD; EGFR; PI3K; SOCS5; cell biology; human; infectious disease; influenza; innate immunity; microbiology; mouse; virus