Transgenic mice carrying hepatitis C Virus genome

为了建立丙型肝炎病毒感染的模型，我们在乙肝病毒调控元件的控制下，通过导入丙型肝炎病毒囊膜基因E1和E2产生转基因小鼠。已经建立的创始人的F1代小鼠在包括肝脏在内的器官中以糖基化形式表达了E1和E2蛋白。免疫组织化学染色显示包膜蛋白主要定位于肝中央静脉周围肝细胞的细胞质中。此外，免疫沉淀显示，在小鼠肝脏中，E1和E2蛋白相互关联。在16个月龄以下的小鼠肝脏中没有组织病理学的证据，这表明E1和E2蛋白本身可能没有直接的致病作用。我们的结果首次证明了丙型肝炎病毒基因产物在小鼠肝脏中的成功表达，并证明了体内表达的丙型肝炎病毒包膜蛋白的相关性。该转基因小鼠可用于研究丙型肝炎病毒与细胞的相互作用，如细胞内转运和囊膜蛋白组装。此外，通过引入针对包膜蛋白的细胞毒性T淋巴细胞，它可能是一个很好的模型系统来确定这些蛋白在肝炎或丙型肝炎感染的肝外表现中的作用。

In an attempt to establish a model for hepatitis C virus infection, we produced transgenic mice by introducing the hepatitis C virus envelope genes, E1 and E2, under the control of a regulatory element from hepatitis B virus. F1-generation mice from the established founders demonstrated expression of both E1 and E2 proteins as glycosylated forms in their organs including the liver. Immunostaining revealed the localization of envelope proteins principally in the cytoplasm of hepatocytes around the hepatic central veins. Furthermore, E1 and E2 proteins were shown by immunoprecipitation to be associated with each other in the mouse liver. There was no evidence of tissue pathology in the mouse liver up to 16 months of age, suggesting that E1 and E2 proteins per se may not have direct pathogenic effects. Our results demonstrate the first successful expression of hepatitis C vircus gene products in the mouse liver and the association of in vivo expressed HCV envelope proteins. This transgenic mouse would be a good model to study the virus-cell interactions of HCV such as intracellular transport and assembly of envelope proteins. Also it may be a good model system to determine the role of these proteins in the pathogenesis of hepatitis or extra-hepatic manifestations in HCV infection with the introduction of cytotoxic T lymphocytes specific for the envelope proteins.