title: HCV core protein interacts with Dicer to antagonize RNA silencing.
abstract: RNA silencing is a form of nucleic acid-based immunity against viruses in plants and invertebrate animals. Successful viral infection requires evasion or suppression of gene silencing. Here, we report that the core protein of Hepatitis C virus (HCV) acts as a potent suppressor of RNA silencing (SRS). We have found that the HCV core protein inhibits RNA silencing induced by short hairpin RNAs (shRNAs) but not by synthetic small interfering RNAs (siRNAs) in various mammalian cells. We have further demonstrated that HCV core protein directly interacts with Dicer, an RNase enzyme that generates siRNA in host cells. The HCV core protein has been shown to inhibit the function of Dicer to process double-stranded RNAs (dsRNAs) into siRNAs. Through deletion analysis, we have found that the N-terminal domain is required for core protein to antagonize RNA silencing activity of Dicer enzyme. Thus, our results suggest that HCV core protein may abrogate host cell RNA silencing defense by suppressing the ability of Dicer to process precursor dsRNAs into siRNAs. This anti-Dicer ability of core protein may contribute to the persistent viral infection and pathogenesis of HCV.
authors.affiliation: The Institute for Viral Hepatitis, Key Laboratory of Molecular Biology on Infectious Diseases of the Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. ache11@163.com
authors.forename: Weixian
authors.initials: W
authors.lastname: Chen
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Xuefei
authors.initials: X
authors.lastname: Cai
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D043244:Ribonuclease III; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D049452:Green Fluorescent Proteins; D008156:Luciferases; D004722:Endoribonucleases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases