title: Golgi protein 73 facilitates the interaction of hepatitis C virus NS5A with apolipoprotein E to promote viral particle secretion.
abstract: Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver diseases and hepatocellular carcinoma (HCC). Golgi protein 73 (GP73), a resident Golgi membrane protein, is a novel serum biomarker for the diagnosis of liver diseases and HCC. Although previous studies have demonstrated that HCV upregulates GP73 expression and GP73 promotes HCV secretion through its interaction with apolipoprotein E (ApoE), the exact mechanism underlying GP73 regulates HCV secretion remains unclear. In this study, we demonstrated that GP73 mediates the interaction of ApoE with HCV NS5A protein to promote HCV secretion. We revealed that GP73 is colocalized with HCV replication complex in infected-Huh7.5.1 cells. Further studies demonstrated that GP73 interacted with both NS5A and ApoE proteins. Furthermore, knockdown of GP73 significantly reduced the binding of NS5A with ApoE, and the production of virus particles in culture supernatant. Taken together, our studies revealed that GP73 promotes HCV secretion by directly mediating the interaction of ApoE with HCV replication complex through binding with HCV NS5A.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Tianci
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Xuechen
authors.initials: X
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Yecheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Kailang
authors.initials: K
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: mvlwu@whu.edu.cn.
authors.forename: Yingle
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Wuhan Medical Treatment Center, Wuhan 430023, China. Electronic address: 13476262815@139.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: jwu@whu.edu.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D006367:HeLa Cells; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014771:Virion / Q000502:physiology*; D019065:Virus Assembly; D057074:Virus Release; D012324:RNA-Dependent RNA Polymerase
chemical_list: D001057:Apolipoproteins E; D008565:Membrane Proteins; D017361:Viral Nonstructural Proteins; C000612345:ApoE protein, human; C410824:GOLM1 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: ApoE; Apolipoprotein E; GP73; Golgi protein 73; HCC; HCV; HCV particle assembly and secretion; Hepatitis C virus; Hepatocellular carcinoma; NS5A; Nonstructural protein 5A