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Elife. 2017 Feb 14;6. pii: e20444. doi: 10.7554/eLife.20444. [Epub ahead of print]
Suppressor of Cytokine Signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.
Kedzierski L1, Tate MD2, Hsu AC3, Kolesnik TB1, Linossi EM1, Dagley L1, Dong Z4, Freeman S1, Infusini G1, Starkey MR3, Bird NL5, Chatfield SM1, Babon JJ6, Huntington N1, Belz G1, Webb A1, Wark PA3, Nicola NA1, Xu J7, Kedzierska K8, Hansbro PM3, Nicholson SE1.
Author information
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) 5 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:
cell biology; human; infectious disease; microbiology; mouse; viruses
PMID: 28195529 DOI: 10.7554/eLife.20444
[PubMed - as supplied by publisher]
Suppressor of Cytokine Signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.
Kedzierski L1, Tate MD2, Hsu AC3, Kolesnik TB1, Linossi EM1, Dagley L1, Dong Z4, Freeman S1, Infusini G1, Starkey MR3, Bird NL5, Chatfield SM1, Babon JJ6, Huntington N1, Belz G1, Webb A1, Wark PA3, Nicola NA1, Xu J7, Kedzierska K8, Hansbro PM3, Nicholson SE1.
Author information
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) 5 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:
cell biology; human; infectious disease; microbiology; mouse; viruses
PMID: 28195529 DOI: 10.7554/eLife.20444
[PubMed - as supplied by publisher]