Lu Yi Wei, Tan Tuan Lin, Chan Vincent, Chen Wei Ning
School of Biological Sciences, College of Engineering, Nanyang Technological University, Singapore 637722, Singapore.
Biochem Biophys Res Commun. 2006 Dec 8;351(1):64-70. doi: 10.1016/j.bbrc.2006.10.002. Epub 2006 Oct 10.
The mechanisms of liver injury in hepatitis B virus (HBV) infection are defined to be due not to the direct cytopathic effects of viruses, but to the host immune response to viral proteins expressed by infected hepatocytes. We showed here that transfection of mammalian cells with a replicative HBV genome causes extensive cytopathic effects, leading to the death of infected cells. While either necrosis or apoptosis or both may contribute to the death of infected cells, results from flow cytometry suggest that apoptosis plays a major role in HBV-induced cell death. Data mining of the four HBV protein sequences reveals the presence of a Bcl-2 homology domain 3 (BH3) in HBSP, a spliced viral protein previously shown to be able to induce apoptosis and associated with HBV pathogenesis. HBSP is expressed at early stage of our cell-based HBV replication. When transfected into HepG2 cells, HBSP causes apoptosis in a caspase dependent manner. Taken together, our results suggested a direct involvement of HBV viral proteins in cellular apoptosis, which may contribute to liver pathogenesis.
乙型肝炎病毒（HBV）感染导致肝损伤的机制被认为并非源于病毒的直接细胞病变效应，而是宿主对受感染肝细胞所表达病毒蛋白的免疫反应。我们在此表明，用复制型HBV基因组转染哺乳动物细胞会导致广泛的细胞病变效应，从而致使受感染细胞死亡。虽然坏死或凋亡或两者都可能导致受感染细胞死亡，但流式细胞术结果表明，凋亡在HBV诱导的细胞死亡中起主要作用。对四种HBV蛋白序列的数据挖掘揭示，在HBSP中存在Bcl-2同源结构域3（BH3），HBSP是一种剪接的病毒蛋白，先前已证明其能够诱导凋亡并与HBV发病机制相关。HBSP在我们基于细胞的HBV复制早期表达。当转染到HepG2细胞中时，HBSP以半胱天冬酶依赖的方式导致凋亡。综上所述，我们的结果表明HBV病毒蛋白直接参与细胞凋亡，这可能导致肝脏发病。
