The development and evaluation of effective therapies and vaccines for the hepatitis C virus (HCV) and the study of its interactions with the mammalian host have been hindered for a long time by the absence of suitable small animal models. Due to the narrow host tropism of HCV, the development of mice that can be robustly engrafted with human hepatocytes was a major breakthrough since they recapitulate the complete HCV life cycle. This model has been useful to investigate many aspects of the HCV life cycle, including antiviral interventions. However, studies of cellular immunity, immunopathogenesis and resulting liver diseases have been hampered by the lack of a small animal model with a functional immune system. In this review, we summarize the evolution of in vivo models for the study of HCV.
