ZEB2 inhibits HBV transcription and replication by targeting its core promoter

Qiao He; Wanyu Li; Jihua Ren; Yecai Huang; Ying Huang; Qin Hu; Juan Chen; Weixian Chen

doi:10.18632/oncotarget.7435

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Research Papers:

ZEB2 inhibits HBV transcription and replication by targeting its core promoter

Qiao He, Wanyu Li, Jihua Ren, Yecai Huang, Ying Huang, Qin Hu, Juan Chen _ and Weixian Chen

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Oncotarget. 2016; 7:16003-16011. https://doi.org/10.18632/oncotarget.7435

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Abstract

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

Correspondence to:

Juan Chen, e-mail: [email protected]

Weixian Chen, e-mail: [email protected]

Keywords: ZEB2, HBV replication, HBV core promoter

Received: October 11, 2015 Accepted: February 05, 2016 Published: February 17, 2016

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.

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Research Papers:

ZEB2 inhibits HBV transcription and replication by targeting its core promoter

Abstract