title: Inducible CYP4F12 enhances Hepatitis C virus infection via association with viral nonstructural protein 5B.
abstract: Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) functions as an RNA-dependent RNA polymerase in the HCV replication complex derived from the endoplasmic reticulum in hepatic cells. In this study, NS5B was used as bait in a yeast two-hybrid assay to screen a human liver cDNA library. We confirmed that CYP4F12, a member of the cytochrome P450 superfamily, interacted with NS5B. Furthermore, overexpression of CYP4F12 facilitated HCV replication. In contrast, knockdown of CYP4F12 by specific shRNA decreased HCV replication and viral protein expression. Moreover, our results demonstrated that HCV infection increased the binding of the transcription factor SREBP1 to the CYP4F12 promoter and activated the promoter activity, which indicated that HCV infection increased the expression of CYP4F12 through the SREBP1 pathway. Our results showed that HCV infection induced expression of CYP4F12 protein, which bound to the HCV replication complex to facilitate viral replication.
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: shenglizhu@whu.edu.cn.
authors: Sheng-Li
authors: SL
authors: Zhu
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: liwang2010@whu.edu.cn.
authors: Li
authors: L
authors: Wang
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: caozhongying@whu.edu.cn.
authors: Zhong-Ying
authors: ZY
authors: Cao
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: wangjun2028@whu.edu.cn.
authors: Jun
authors: J
authors: Wang
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: jingmingzhen@whu.edu.cn.
authors: Ming-Zhen
authors: MZ
authors: Jing
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: xiazhangchuan@whu.edu.cn.
authors: Zhang-Chuan
authors: ZC
authors: Xia
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: 87310026@qq.com.
authors: Fang
authors: F
authors: Ao
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: linbaiye@whu.edu.cn.
authors: Lin-Bai
authors: LB
authors: Ye
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: liushi_liushi@whu.edu.cn.
authors: Shi
authors: S
authors: Liu
authors: State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: yingzhu@whu.edu.cn.
authors: Ying
authors: Y
authors: Zhu
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism / Q000821:virology; D006801:Humans; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D017361:Viral Nonstructural Proteins; C422180:CYP4F12 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: CYP4F12; Hepatitis C virus; Viral replication