Pathogenesis of liver injury and carcinogenesis in HCV-expressing model animals by in vivo gene transfer.

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The lack of small animal model of hepatitis C virus (HCV) infection impeded elucidation of the pathogenesis of this virus. The aim of this study is to develop HCV-expressing model animals using in vivo gene transfer and use them to study the pathogenesis of liver injury and hepatocarcinogenesis. In this study, we used cationic liposome-mediated and asialoglycoprotein receptor-mediatd in vivo gene transfer. To examine the feasibility of these procedures, pActLacZ in which the LacZ gene was driven by the beta-actin promoter was used as an reporter vector and successful transfection into rat hepatocytes in vivo was confermed by X-Gal histochemistry. For expression of HCV,HCV-expression vector in which the full-coding sequence of the HCV genome was driven by the beta-actin promoter was used. The expression of HCV in rat hepatocytes in vivo was confermed by RT/PCR and immunohistochemical staining using anti-HCV core monoclonal antibody. These HCV-expressing model rats will be useful for determining the pathological role of HCV in vivo.