ZEB2 inhibits HBV transcription and replication by targeting its core promoter
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Qiao He1,*, Wanyu Li2,*, Jihua Ren2, Yecai Huang3, Ying Huang4, Qin Hu1, Juan Chen2, Weixian Chen1
1Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
2The 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
3Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, China
4Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
*These authors have contributed equally to this work
Juan Chen, e-mail: firstname.lastname@example.org
Weixian Chen, e-mail: email@example.com
Keywords: ZEB2, HBV replication, HBV core promoter
Received: October 11, 2015 Accepted: February 05, 2016 Published: February 17, 2016
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.
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