长链非编码RNA HNF4A-AS1上调TLE4抑制乙型肝炎病毒复制。

IF 2.7 4区医学 Q3 VIROLOGY

Virus research Pub Date : 2025-08-14 DOI:10.1016/j.virusres.2025.199616

Lihua Liu , Wenxiu Dai , Qinghui Wang , Huizhong Qian , Xiao Liu , Qingqin Hao

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引用次数: 0

摘要

新出现的证据表明，长链非编码rna （lncRNAs）参与乙型肝炎病毒（HBV）的复制。然而，大多数lncrna在HBV复制中的作用尚不清楚。在本研究中，我们确定HNF4A-AS1在感染期间被HBV下调。有趣的是，HNF4A-AS1抑制HBV在人肝癌细胞中的转录和复制。在机制上，HNF4A-AS1通过在转录水平上促进TLE4的表达来抑制HBV复制。TLE4 WD-repeat结构域是TLE4介导的抗hbv活性所必需的。总之，我们的研究结果揭示了HBV复制和HNF4A-AS1表达的负反馈机制，并确定HNF4A-AS1是HBV复制的一种新的宿主限制因子，为HBV治疗提供了潜在的治疗靶点。

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Long noncoding RNA HNF4A-AS1 upregulates TLE4 to inhibit hepatitis B virus replication

Emerging evidence has revealed that long noncoding RNAs (lncRNAs) are involved in hepatitis B virus (HBV) replication. However, the roles of most lncRNAs in HBV replication remain unclear. In the present study, we determined that HNF4A-AS1 was downregulated by HBV during infection. Interestingly, HNF4A-AS1 inhibited HBV transcription and replication in human hepatoma cells. Mechanistically, HNF4A-AS1 inhibited HBV replication by promoting TLE4 expression at the transcriptional level. The TLE4 WD-repeat domain is required for TLE4-mediated anti-HBV activity. Collectively, our findings have uncovered a negative feedback mechanism underlying HBV replication and HNF4A-AS1 expression and identify HNF4A-AS1 as a novel host restriction factor in HBV replication, providing a potential therapeutic target for HBV treatment.

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来源期刊

Virus research 医学-病毒学

CiteScore

9.50

自引率

2.00%

发文量

239

审稿时长

43 days

期刊介绍： Virus Research provides a means of fast publication for original papers on fundamental research in virology. Contributions on new developments concerning virus structure, replication, pathogenesis and evolution are encouraged. These include reports describing virus morphology, the function and antigenic analysis of virus structural components, virus genome structure and expression, analysis on virus replication processes, virus evolution in connection with antiviral interventions, effects of viruses on their host cells, particularly on the immune system, and the pathogenesis of virus infections, including oncogene activation and transduction.