title: Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33.
abstract: Viperin is a type-I and -II interferon-inducible intracytoplasmic protein that mediates antiviral activity against several viruses. A previous study has reported that viperin could limit hepatitis C virus (HCV) replication in vitro. However, the underlying mechanism remains elusive. In the present study, we found that overexpression of viperin could inhibit HCV replication in a dose-dependent manner in both the replicon and HCVcc systems. Furthermore, through co-immunoprecipitation and laser confocal microscopic analysis, viperin was found to interact with the host protein hVAP-33. Mutagenesis analysis demonstrated that the anti-HCV activity of viperin was located to its C terminus, which was required for the interaction with the C-terminal domain of hVAP-33. Competitive co-immunoprecipitation analysis showed that viperin could interact competitively with hVAP-33, and could therefore interfere with its interactions with HCV NS5A. In summary, these findings suggest a novel mechanism by which viperin inhibits HCV replication, possibly through binding to host protein hVAP-33 and interfering with its interaction with NS5A.
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors.forename: Wuhui
authors.initials: W
authors.lastname: Song
authors.affiliation: Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D006801:Humans; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000090123:Viperin Protein; D012324:RNA-Dependent RNA Polymerase
chemical_list: D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; D033921:Vesicular Transport Proteins; D017361:Viral Nonstructural Proteins; C114051:VAPA protein, human; C444427:RSAD2 protein, human; D000090123:Viperin Protein; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase