title: A functional role for NS5ATP9 in the induction of HCV NS5A-mediated autophagy.
abstract: Autophagy has been shown to facilitate replication of hepatitis C virus (HCV); however, the mechanism by which HCV induces autophagy has not been fully established. NS5A, a nonstructural protein expressed by HCV, regulates numerous cellular pathways, including autophagy, by up-regulating Beclin 1; however, the underlying mechanism remains unclear. To obtain new insights into HCV-regulated autophagy, NS5ATP9 was overexpressed in HepG2 and L02 cells, resulting in up-regulation of endogenous Beclin 1 mRNA and protein levels, respectively. The luciferase-reporter assay results showed that both NS5A and NS5ATP9 could transactivate Beclin 1 promoter activity, but that NS5A could not transactivate the Beclin 1 promoter in NS5ATP9-silenced HepG2 and L02 cells. Up-regulation of Beclin 1 mRNA and protein expression by NS5A could also be attenuated by NS5ATP9 knock-down. Furthermore, the HepG2 and L02 cells that transiently overexpressed NS5ATP9 had enhanced accumulation of vacuoles carrying the autophagy marker LC3, consistent with the conversion of endogenous LC3-I to LC3-II. In contrast, the conversion of endogenous LC3-I to LC3-II could not be enhanced by NS5A in NS5ATP9-silenced HepG2 cells. These results highlight an important potential role for NS5ATP9 in HCV NS5A-induced hepatocyte autophagy.
authors.affiliation: Beijing Ditan Hospital, Peking University Teaching Hospital, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Quan
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Gao
authors.forename: S
authors.initials: S
authors.lastname: Feng
authors.forename: J
authors.initials: J
authors.lastname: Cheng
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy; D000071186:Beclin-1; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D017361:Viral Nonstructural Proteins; C491997:BECN1 protein, human; C425208:PCLAF protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Beclin 1; HCV; LC3; NS5A; NS5ATP9; autophagy