title: ZEB2 inhibits HBV transcription and replication by targeting its core promoter.
abstract: Hepatitis B virus (HBV) infection is a major cause of liver diseases, especially liver cirrhosis and hepatocellular carcinoma. However, the interaction between host and HBV has not been fully elucidated. ZEB2 is a Smad-interacting, multi-zinc finger protein that acts as a transcription factor or repressor for several signaling pathways. This study found that the expression of ZEB2 was decreased in HBV-expressing cells. Overexpression of ZEB2 inhibited HBV DNA replicative intermediates, 3.5kb mRNA, core protein level, and the secretion of HBsAg and HBeAg. In contrast, ZEB2 knockdown promoted HBV replication. Furthermore, ZEB2 could bind to HBV core promoter and inhibit its promoter activity. Mutation at the ZEB2 binding site in HBV core promoter eradicated ZEB2-mediated inhibition of HBV replication. This study identifies ZEB2 as a novel host restriction factor that inhibits HBV replication in hepatocytes. These data may shed light on development of new antiviral strategies.
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: He
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology of Infectious Diseases designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Wanyu
authors.initials: W
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology of Infectious Diseases designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, China.
authors.forename: Yecai
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology of Infectious Diseases designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Weixian
authors.initials: W
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*; D000074165:Zinc Finger E-box Binding Homeobox 2 / Q000378:metabolism*
chemical_list: D014758:Viral Core Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2
keywords: HBV core promoter; HBV replication; ZEB2