Mechanism of Hepatitis B Virus cccDNA Formation.

Mechanism of Hepatitis B Virus cccDNA Formation.
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DOI:
10.3390/v13081463
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发表时间:
2021-07-27
期刊:
Viruses
影响因子:
--
通讯作者:
Ploss A
Ploss A
中科院分区:
其他
文献类型:
--
作者:
Wei L;Ploss A

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乙型肝炎病毒(HBV)仍然是一个主要的医疗问题,影响着至少2.57亿慢性感染患者,这些患者有发展为严重且往往致命的肝脏疾病的风险。HBV是一种小的部分双链DNA病毒,在其原生细胞环境(人肝细胞)中经历一个复杂的复制周期。病毒生命周期中的一个关键步骤是将松弛环状DNA (rcDNA)转化为共价闭合环状DNA (cccDNA),后者是HBV基因转录的主要模板。对于这种转化,HBV依赖于多种宿主因子,因为能够催化相关反应的酶没有在病毒基因组中编码。遗传和生化方法的结合已经产生的发现提供了HBV cccDNA形成复杂机制的更全面的图景。在这里,我们回顾了一些有助于提供rcDNA到cccDNA转换的全面图景的研究。对HBV持久性这一关键步骤的机制洞察是设计新疗法的关键,这些新疗法不仅可以抑制病毒,还可以治愈病毒。
Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are at risk of developing serious, frequently fatal liver diseases. HBV is a small, partially double-stranded DNA virus that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step in the viral life-cycle is the conversion of relaxed circular DNA (rcDNA) into covalently closed circular DNA (cccDNA), the latter being the major template for HBV gene transcription. For this conversion, HBV relies on multiple host factors, as enzymes capable of catalyzing the relevant reactions are not encoded in the viral genome. Combinations of genetic and biochemical approaches have produced findings that provide a more holistic picture of the complex mechanism of HBV cccDNA formation. Here, we review some of these studies that have helped to provide a comprehensive picture of rcDNA to cccDNA conversion. Mechanistic insights into this critical step for HBV persistence hold the key for devising new therapies that will lead not only to viral suppression but to a cure.
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