title: Hepatitis C virus NS5A protein modulates IRF-7-mediated interferon-α signaling.
abstract: 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.
authors: 1 Department of Pathology, Edward A. Doisy Research Center, Saint Louis University , St. Louis, Missouri.
authors: Joydip Bhanja
authors: JB
authors: Chowdhury
authors: Hangeun
authors: H
authors: Kim
authors: Ranjit
authors: R
authors: Ray
authors: Ratna B
authors: RB
authors: Ray
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism*; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
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