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Hepatitis C virus core protein induces an anergic state characterized by decreased interleukin-2 production and perturbation of mitogen-activated protein kinase responses
Karolinska Institutet.
Karolinska Institutet.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Karolinska Institutet.
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2005 (English)In: Journal of Virology, ISSN 0022-538X, Vol. 79, no 4, 2230-2239 p.Article in journal (Refereed) Published
Abstract [en]

Alterations of cytokine responses are thought to favor the establishment of persistent hepatitis C virus (HCV) infections, enhancing the risk of liver cirrhosis and hepatocellular carcinoma. Here we demonstrate that the expression of the HCV core (C) protein in stably transfected T cells correlates with a selective reduction of interleukin-2 (IL-2) promoter activity and IL-2 production in response to T-cell receptor triggering, whereas the activation of IL-4, IL-10, gamma interferon, and tumor necrosis factor alpha was moderately increased. This altered cytokine expression profile was associated with a perturbation of mitogen-activated protein (MAP) kinase responses. Extracellular regulated kinase and p38 were constitutively phosphorylated in C-expressing cells, while triggering of the costimulatory c-Jun N-terminal kinase (JNK) signaling cascade and activation of the CD28 response element within the IL-2 promoter appeared to be impaired. The perturbations of MAP kinase phosphorylation could be eliminated by cyclosporine A-mediated inhibition of nuclear factor of activated T cells, suggesting that the inactivation of JNK signaling and hyporesponsiveness to IL-2 induction were downstream consequences of C-induced Ca2+ flux in a manner that mimics the induction of clonal anergy.

Place, publisher, year, edition, pages
2005. Vol. 79, no 4, 2230-2239 p.
National Category
Medical and Health Sciences Microbiology in the medical area Microbiology in the medical area
Research subject
Medical Virology
URN: urn:nbn:se:uu:diva-86667DOI: 10.1128/JVI.79.4.2230-2239.2005PubMedID: 15681425OAI: oai:DiVA.org:uu-86667DiVA: diva2:126849
Available from: 2008-11-27 Created: 2008-11-24 Last updated: 2009-05-26Bibliographically approved

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Bergqvist, Anders
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