Allweiss Lena, Dandri Maura
I. Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
German Center for Infection Research (DZIF), Hamburg-Lübeck-Borstel Site, Germany.
Viruses. 2017 Jun 21;9(6):156. doi: 10.3390/v9060156.
Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development of liver cirrhosis and hepatocellular carcinoma. The molecular mechanisms determining HBV persistence are not fully understood, but these appear to be multifactorial and the unique replication strategy employed by HBV enables its maintenance in infected hepatocytes. Both the stability of the HBV genome, which forms a stable minichromosome, the covalently closed circular DNA (cccDNA) in the hepatocyte nucleus, and the inability of the immune system to resolve chronic HBV infection are believed to be key mechanisms of HBV chronicity. Since a true cure of HBV requires clearance of intranuclear cccDNA from infected hepatocytes, understanding the mechanisms involved in cccDNA biogenesis, regulation and stability is mandatory to achieve HBV eradication. This review will summarize the state of knowledge on these mechanisms including the impact of current treatments on the cccDNA stability and activity. We will focus on events challenging cccDNA persistence in dividing hepatocytes.
慢性乙型肝炎病毒（HBV）感染仍然是全球主要的健康负担；它可导致不同程度的肝损伤，并与肝硬化和肝细胞癌的发生密切相关。决定HBV持续存在的分子机制尚未完全明确，但这些机制似乎是多因素的，并且HBV采用的独特复制策略使其能够在受感染的肝细胞中维持。HBV基因组的稳定性（其在肝细胞核中形成稳定的微型染色体，即共价闭合环状DNA [cccDNA]）以及免疫系统无法清除慢性HBV感染，都被认为是HBV慢性化的关键机制。由于真正治愈HBV需要从受感染的肝细胞中清除核内cccDNA，因此了解参与cccDNA生物合成、调控和稳定性的机制对于实现HBV根除至关重要。本综述将总结关于这些机制的知识现状，包括当前治疗对cccDNA稳定性和活性的影响。我们将重点关注挑战cccDNA在分裂肝细胞中持续存在的事件。
