Mouse models for the study of HCV infection and virus-host interactions

Abstract

Hepatitis C virus (HCV) is a major cause of chronic liver disease including steatosis, cirrhosis and hepatocellular carcinoma. The development of transgenic mice expressing HCV proteins and the successful repopulation of SCID/Alb-uPA mice with human hepatocytes provides an important tool for unraveling virus-host interactions in vivo. Several of these mouse models exhibit aspects of HCV-related liver disease. Thus, these in vivo models play an important role to further understand the pathogenesis of HCV infection and to evaluate the pre-clinical safety and efficacy of new antiviral compounds against HCV. This review summarizes the most important mouse models currently used to study HCV pathogenesis and infection. Finally, the perspective of these models for future HCV research as well as the design of novel small animal models is discussed.

Fig. 1

Chimeric transgenic mice repopulated with human hepatocytes for the study of HCV infection. Hemizygous Alb-uPA mice were crossed to homozygosity with homozygous SCID/bg mice. The resulting Alb-uPA/SCID mice can be transplanted with human hepatocytes and support HCV infection from human infected-serum or recombinant cell culture-derived HCV (HCVcc). This model has been successfully used to study virus–host interactions in infected hepatocytes as well as the evaluation of antiviral strategies including antiviral drugs and monoclonal antibodies. The evaluation of cell therapy products may represent another application of this model in the future.