ZEB2 inhibits HBV transcription and replication by targeting its core promoter.
ZEB2 inhibits HBV transcription and replication by targeting its core promoter.
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DOI：
10.18632/oncotarget.7435
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发表时间：
2016-03-29
期刊：
影响因子：
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通讯作者：
Chen W
中科院分区：
文献类型：
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作者：
He Q;Li W;Ren J;Huang Y;Huang Y;Hu Q;Chen J;Chen W
乙型肝炎病毒（HBV）感染是肝脏疾病的主要原因，尤其是肝硬化和肝细胞癌。然而，宿主与HBV之间的相互作用尚未完全阐明。ZEB2是一种与smad相互作用的多锌指蛋白，可作为多种信号通路的转录因子或抑制因子。本研究发现，在hbv表达的细胞中，ZEB2的表达降低。过表达ZEB2抑制HBV DNA复制中间体、3.5kb mRNA、核心蛋白水平，抑制HBsAg和HBeAg的分泌。相反，ZEB2敲低促进HBV复制。此外，ZEB2可以结合HBV核心启动子并抑制其启动子活性。HBV核心启动子中ZEB2结合位点的突变消除了ZEB2介导的HBV复制抑制。本研究发现ZEB2是一种抑制HBV在肝细胞复制的新型宿主限制因子。这些数据可能有助于开发新的抗病毒策略。
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.