Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS, Université de Montpellier, UMR9002 Montpellier, France.
Viruses. 2021 Apr 26;13(5):757. doi: 10.3390/v13050757.
Hepatitis B virus (HBV) remains a major public health concern, with more than 250 million chronically infected people who are at high risk of developing liver diseases, including cirrhosis and hepatocellular carcinoma. Although antiviral treatments efficiently control virus replication and improve liver function, they cannot cure HBV infection. Viral persistence is due to the maintenance of the viral circular episomal DNA, called covalently closed circular DNA (cccDNA), in the nuclei of infected cells. cccDNA not only resists antiviral therapies, but also escapes innate antiviral surveillance. This viral DNA intermediate plays a central role in HBV replication, as cccDNA is the template for the transcription of all viral RNAs, including pregenomic RNA (pgRNA), which in turn feeds the formation of cccDNA through a step of reverse transcription. The establishment and/or expression of cccDNA is thus a prime target for the eradication of HBV. In this review, we provide an update on the current knowledge on the initial steps of HBV infection, from the nuclear import of the nucleocapsid to the formation of the cccDNA.
乙型肝炎病毒 (HBV) 仍然是一个主要的公共卫生关注点，全球有超过 2.5 亿慢性感染者，他们面临着发展为肝脏疾病（包括肝硬化和肝细胞癌）的高风险。尽管抗病毒治疗可以有效地控制病毒复制并改善肝功能，但它们无法治愈 HBV 感染。病毒持续存在是由于感染细胞核内的病毒环状游离 DNA（cccDNA）的维持。cccDNA 不仅抵抗抗病毒治疗，还逃避了先天抗病毒监测。这种病毒 DNA 中间体在 HBV 复制中起着核心作用，因为 cccDNA 是所有病毒 RNA 转录的模板，包括前基因组 RNA（pgRNA），pgRNA 反过来通过逆转录的一个步骤为 cccDNA 的形成提供原料。因此，cccDNA 的建立和/或表达是根除 HBV 的主要目标。在这篇综述中，我们提供了关于 HBV 感染初始步骤的最新知识，包括核衣壳的核内输入到 cccDNA 的形成。
