Metabolism and function of hepatitis B virus cccDNA: Implications for the development of cccDNA-targeting antiviral therapeutics.
Metabolism and function of hepatitis B virus cccDNA: Implications for the development of cccDNA-targeting antiviral therapeutics.
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DOI：
10.1016/j.antiviral.2015.08.005
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发表时间：
2015-10
影响因子：
7.6
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Guo JT;Guo H
持续性B型肝炎病毒（HBV）感染依赖于称为共价闭合环状（ccc）DNA的病毒基因组的核附加体形式的稳定维持和正常功能。目前可用的抗病毒治疗剂未能治愈慢性HBV感染的主要原因之一是它们不能根除或消除cccDNA。在这篇综述文章中，我们总结了我们目前对肝细胞中cccDNA代谢的理解以及宿主病理生理学和免疫学线索对cccDNA的调节。还讨论了cccDNA生物学未来研究的前景，以及通过合理设计和表型筛选治疗性消除和/或转录沉默cccDNA的策略和进展。这篇文章是抗病毒研究专题讨论会的一部分，主题是“一个未完成的故事：从澳大利亚抗原的发现到B型肝炎新治疗方法的发展”。
Persistent hepatitis B virus (HBV) infection relies on the stable maintenance and proper functioning of a nuclear episomal form of the viral genome called covalently closed circular (ccc) DNA. One of the major reasons for the failure of currently available antiviral therapeutics to achieve a cure of chronic HBV infection is their inability to eradicate or inactivate cccDNA. In this review article, we summarize our current understanding of cccDNA metabolism in hepatocytes and the modulation of cccDNA by host pathophysiological and immunological cues. Perspectives on the future investigation of cccDNA biology, as well as strategies and progress in therapeutic elimination and/or transcriptional silencing of cccDNA through rational design and phenotypic screenings, are also discussed. This article forms part of a symposium in Antiviral Research on “An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.”