Hu Jianming, Seeger Christoph
Department of Microbiology and Immunology, Penn State University College of Medicine, Hershey, Pennsylvania 17033.
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Cold Spring Harb Perspect Med. 2015 Jul 1;5(7):a021386. doi: 10.1101/cshperspect.a021386.
Hallmarks of the hepadnavirus replication cycle are the formation of covalently closed circular DNA (cccDNA) and the reverse transcription of a pregenomic RNA (pgRNA) in core particles leading to synthesis of the relaxed circular DNA (rcDNA) genome. cccDNA, the template for viral RNA transcription, is the basis for the persistence of these viruses in infected hepatocytes. In this review, we summarize the current state of knowledge on the mechanisms of hepadnavirus reverse transcription and the biochemical and structural properties of the viral reverse transcriptase (RT). We highlight important gaps in knowledge regarding cccDNA biosynthesis and stability. In addition, we discuss the impact of current antiviral therapies on viral persistence, particularly on cccDNA.
嗜肝DNA病毒复制周期的标志是共价闭合环状DNA（cccDNA）的形成以及前基因组RNA（pgRNA）在核心颗粒中的逆转录，从而导致松弛环状DNA（rcDNA）基因组的合成。cccDNA作为病毒RNA转录的模板，是这些病毒在受感染肝细胞中持续存在的基础。在本综述中，我们总结了关于嗜肝DNA病毒逆转录机制以及病毒逆转录酶（RT）的生化和结构特性的当前知识状态。我们强调了关于cccDNA生物合成和稳定性方面的重要知识空白。此外，我们讨论了当前抗病毒疗法对病毒持续存在的影响，特别是对cccDNA的影响。
