Novel HCV replication mouse model using human hepatocellular carcinoma xenografts

Abstract

In the absence of an immunocompetent mouse model for HCV replication, we developed a convenient xenograft mouse model that produces infectious viral particles. For this purpose, HCV-permissive tumors were generated in SCID/beige mice using a tumorigenic population of the human hepatocarcinoma-derived Huh7 cell line. Following infection, HCV RNA increased in the mouse sera and the human tumor by up to 10(5)GE/ml and 10(7)GE/microg of RNA, respectively. Immunohistochemistry analysis revealed that active viral replication had taken place within the tumor. Moreover, virus recovered from infected mice sera was readily infectious in cell culture. Finally, we showed that interferon-alpha and the protease inhibitor BILN-2061 inhibited the cell culture HCVcc strain JFH1 replication in vivo. In conclusion, we developed a simple and inexpensive mouse model that allows the production of infectious HCV particles in vivo. Such a model will be an extremely valuable tool for the characterization of promising drug candidates.