Favre Daniel, Petit Marie-Anne, Trépo Christian
INSERM, Virus des Hépatites et Pathologies Associées, F-Lyon.
ALTEX. 2003;20(3):131-42.
Hepatitis B virus (HBV) is the major cause of chronic liver disease and hepatocellular carcinoma in the world, with more than 400 million people infected worldwide. To date, there is no reliable model for the study of the many aspects of HBV infection, despite the use of the chimpanzee. Although several alternative methods have been previously developed for the in vitro study of HBV infection, there is still an urgent need for new in vitro infection models, including for the ability of HBV to integrate into the host cell genome. Here we describe a process to improve infection of the human hepatoma cell lines HepG2 and HuH-7 in vitro with HBV originating from human blood. As shown previously for infection of hepatocytes with hepatitis C virus (HCV), the removal of the cell-bound lipoproteins prior to the addition of the viral inoculum to the cells could also be critical for the uptake of HBV via lipoprotein (LDL)-related receptors. Induction by insulin and dexamethasone led to an increase of HBsAg expression at the cell surface in association with the integration of the viral DNA into the host genome and HBx RNA detection. This integration process was also shown to be associated with cytopathic changes and further phenotypic transformations of the cells.
乙型肝炎病毒（HBV）是全球慢性肝病和肝细胞癌的主要病因，全球有超过4亿人感染。迄今为止，尽管使用了黑猩猩，但仍没有可靠的模型用于研究HBV感染的诸多方面。虽然此前已经开发了几种用于体外研究HBV感染的替代方法，但仍迫切需要新的体外感染模型，包括研究HBV整合到宿主细胞基因组中的能力。在此，我们描述了一种改进源自人血液的HBV体外感染人肝癌细胞系HepG2和HuH-7的方法。如先前关于丙型肝炎病毒（HCV）感染肝细胞的研究所示，在向细胞添加病毒接种物之前去除细胞结合的脂蛋白对于通过脂蛋白（LDL）相关受体摄取HBV也可能至关重要。胰岛素和地塞米松诱导导致细胞表面HBsAg表达增加，同时病毒DNA整合到宿主基因组中并检测到HBx RNA。还显示这种整合过程与细胞病变变化和细胞的进一步表型转化有关。
