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J Interferon Cytokine Res. 2014 Jan;34(1):16-21. doi: 10.1089/jir.2013.0038. Epub 2013 Aug 20.

Hepatitis C virus NS5A protein modulates IRF-7-mediated interferon-α signaling.

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  • 11 Department of Pathology, Edward A. Doisy Research Center, Saint Louis University , St. Louis, Missouri.


Hepatitis C virus (HCV) establishes chronic infection in a large number of infected individuals. We have previously shown that HCV infection in hepatocytes blocks poly (I-C) or interferon (IFN)-α-mediated IRF-7 nuclear translocation (Raychoudhuri and others 2010). However, the mechanism of IRF-7 regulation by HCV remained unknown. In this study, we have observed that HCV NS5A physically associates with IRF-7. A subsequent study suggested that the HCV NS5A protein blocks IRF-7-mediated IFN-α14 promoter activation. Further analyses demonstrated that site-specific mutagenesis of the 2 basic arginine residues (amino acids Arg(216) and Arg(217)) in the NS5A is critical for IRF-7-mediated IFN-α14 promoter regulation. Together, our results suggested that the HCV NS5A protein limits the IFN-α-signaling pathway in association with IRF-7, and may, in part, be responsible for the establishment of chronic infection.

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