School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.
Virology. 2013 Nov;446(1-2):357-64. doi: 10.1016/j.virol.2013.08.014. Epub 2013 Sep 13.
Nucleos(t)ide analogues that inhibit hepatitis B virus (HBV) DNA replication are typically used as monotherapy for chronically infected patients. Treatment with a nucleos(t)ide analogue eliminates most HBV DNA replication intermediates and produces a gradual decline in levels of covalently closed circular DNA (cccDNA), the template for viral RNA synthesis. It remains uncertain if levels of cccDNA decline primarily through hepatocyte death, or if loss also occurs during hepatocyte mitosis. To determine if cccDNA survives mitosis, growing ducklings infected with duck hepatitis B virus (DHBV) were treated with the nucleoside analogue, Entecavir. Viremia was suppressed at least 10(5)-fold, during a period when average liver mass increased 23-fold. Analysis of the data suggested that if cccDNA synthesis was completely inhibited, at least 49% of cccDNA survived hepatocyte mitosis. However, there was a large duck-to-duck variation in cccDNA levels, suggesting that low level cccDNA synthesis may contribute to this apparent survival through mitosis.
核苷（酸）类似物能抑制乙型肝炎病毒 (HBV) DNA 复制，通常被用于慢性感染患者的单药治疗。核苷（酸）类似物治疗能消除大部分 HBV DNA 复制中间体，并导致共价闭合环状 DNA（cccDNA）水平逐渐下降，cccDNA 是病毒 RNA 合成的模板。目前尚不清楚 cccDNA 的减少主要是通过肝细胞死亡，还是在肝细胞有丝分裂过程中发生丢失。为了确定 cccDNA 是否能在有丝分裂中存活，我们用核苷类似物恩替卡韦（Entecavir）处理感染鸭乙型肝炎病毒（DHBV）的雏鸭。在至少 10(5)倍的病毒血症抑制期间，平均肝质量增加了 23 倍。数据分析表明，如果 cccDNA 合成完全被抑制，至少有 49%的 cccDNA 在肝细胞有丝分裂中存活。然而，在鸭与鸭之间 cccDNA 水平存在很大差异，这表明低水平的 cccDNA 合成可能通过有丝分裂导致这种明显的存活。
