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    Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses


    Collins, Aideen S. and Ahmed, Suaad and Napoletano, Silvia and Schroeder, Martina and Johnston, James A. and Hegarty, John E. and O'Farrelly, Cliona and Stevenson, Nigel J. (2014) Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses. Journal of Leukocyte Biology, 96 (2). pp. 255-263. ISSN 0741-5400

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    Abstract

    TNF-α is a proinflammatory cytokine, dramatically elevated during pathogenic infection and often responsible for inflammation-induced disease pathology. SOCS proteins are inhibitors of cytokine signaling and regulators of inflammation. In this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF-α and negatively regulate its NF-κB-mediated signal transduction. We discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3 expression but less TNF-α-mediated IκB degradation and proinflammatory cytokine production than healthy controls. HCV protein expression in Huh7 hepatocytes also induced SOCS3 and directly inhibited TNF-α-mediated IL-8 production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits TRAF2-mediated NF-κB promoter activity, suggesting a mechanism by which SOCS3 inhibits TNF-α-mediated signaling. These results demonstrate a role for SOCS3 in regulating proinflammatory TNF-α signal transduction and reveal a novel immune-modulatory mechanism by which HCV suppresses inflammatory responses in primary immune cells and hepatocytes, perhaps explaining mild pathology often associated with acute HCV infection.

    Item Type: Article
    Additional Information: The definitive published version of this article is available at 10.1189/jlb.2A1211-608RRRR
    Keywords: viral infection; inflammation; signal transduction; peripheral blood mononuclear cells; hepatocytes;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 6918
    Identification Number: https://doi.org/10.1189/jlb.2A1211-608RRRR
    Depositing User: Martina Schroeder
    Date Deposited: 22 Jan 2016 16:18
    Journal or Publication Title: Journal of Leukocyte Biology
    Publisher: Society for Leukocyte Biology
    Refereed: Yes
    Funders: Health Research Board (HRB), Northern Ireland Research & Development Office
    URI:

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