Human hepatitis B virus (HBV) infection is the major cause of acute and chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. Although the application of prophylactic vaccination programs has successfully prevented the trend of increasing HBV infection prevalence, the number of HBV-infected people remains very high. Approved therapeutic management efficiently suppresses viral replication; however, HBV infection is rarely completely resolved. The major reason for therapeutic failure is the persistence of covalently closed circular DNA (cccDNA), which forms viral minichromosomes by combining with histone and nonhistone proteins in the nucleus. Increasing evidence indicates that chromatin-modifying enzymes, viral proteins, and noncoding RNAs are essential for modulating the function of cccDNA. Therefore, a deeper understanding of the regulatory mechanism underlying cccDNA transcription will contribute to the development of a cure for chronic hepatitis B. This review summarizes the current knowledge of cccDNA biology, the regulatory mechanisms underlying cccDNA transcription, and novel anti-HBV approaches for eliminating cccDNA transcription.

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乙型肝炎病毒共价闭合环状DNA的表观遗传调控及其治疗潜力

人类乙型肝炎病毒（HBV）感染是急慢性乙型肝炎、肝硬化和肝细胞癌的主要原因。尽管预防性疫苗接种计划的应用成功阻止了乙型肝炎病毒感染率上升的趋势，但乙型肝炎病毒感染人数仍然很高。经批准的治疗管理可有效抑制病毒复制；然而，乙型肝炎病毒感染很少能完全解决。治疗失败的主要原因是共价闭合环状 DNA (cccDNA) 的持续存在，它通过与细胞核中的组蛋白和非组蛋白结合形成病毒微型染色体。越来越多的证据表明染色质修饰酶、病毒蛋白和非编码 RNA 对于调节 cccDNA 的功能至关重要。因此，更深入地了解 cccDNA 转录的调控机制将有助于开发治疗慢性乙型肝炎的药物。这篇综述总结了 cccDNA 生物学的最新知识、cccDNA 转录的调控机制以及消除乙型肝炎的新型抗乙肝方法。 cccDNA 转录。