ZEB2 inhibits HBV transcription and replication by targeting its core promoter

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 rep...

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Bibliographic Details
Published in:Oncotarget 2016-03, Vol.7 (13), p.16003-16011
Main Authors: He, Qiao, Li, Wanyu, Ren, Jihua, Huang, Yecai, Huang, Ying, Hu, Qin, Chen, Juan, Chen, Weixian
Format: Article
Language:English
Subjects:
Cell Line
Hepatitis B - virology
Hepatitis B virus - physiology
Hepatocytes - metabolism
Hepatocytes - virology
Host-Pathogen Interactions - physiology
Humans
Promoter Regions, Genetic - physiology
Research Paper
Transcription, Genetic
Viral Core Proteins - metabolism
Virus Replication - physiology
Zinc Finger E-box Binding Homeobox 2 - metabolism
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.7435