In the context of pathogenesis of HBV infection, HBV genotypes and mutants have been shown to affect the natural course of chronic infection and treatment outcomes. In this work, we studied the induction of apoptosis by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. Both subgenotypes F1b and F4 HBV genome transfections induced cell death by apoptosis in human hepatocytes. The BCPdm (A1762T/G1764A) and preCore (G1896A) mutants induced higher levels of apoptosis than the wt virus. This increase in apoptosis was not associated with the enhanced viral replication of the variants. HBV-mediated apoptosis was independent of viral subgenotypes, and associated with the modulation of members of the regulatory Bcl-2 family proteins expression in the mitochondrial apoptotic pathway. Finally, the apoptosis induction increase observed for the preCore mutants suggests that HBeAg might have an anti-apoptotic effect in human hepatocytes.

在HBV感染的发病机制中，已证明HBV基因型和突变体会影响慢性感染和治疗结果的自然过程。在这项工作中，我们研究了通过复制HBV亚型F1b和F4以及自然发生的突变体BCP和preCore来诱导凋亡。F1b和F4 HBV亚基因型基因组转染均通过人肝细胞凋亡诱导细胞死亡。BCPdm（A1762T / G1764A）和preCore（G1896A）突变体比wt病毒诱导更高水平的凋亡。凋亡的这种增加与变体的病毒复制增强无关。HBV介导的细胞凋亡与病毒亚基因型无关，并且与线粒体凋亡途径中调节性Bcl-2家族蛋白表达的成员相关。最后，