Advances in our understanding of two major human pathogens, hepatitis B virus (HBV) and hepatitis C virus (HCV), have been limited by a lack of suitable model systems for their study. Surrogate systems such as HBV recombinant baculoviruses have been developed to allow in vitro studies of HBV biology in the face of a lack of cell lines permissive to infection by this agent. The generation of infectious HCV culture systems has also allowed progress in the study of HCV virology. However, restriction of tropism of the available ICG-001 cell culture infectious HCV strains to hepatocellular carcinoma cell lines has constrained
the general applicability of findings from these systems to events occurring in infected primary hepatocytes. The recent development of a model in which primary human hepatocytes have been shown to be rendered susceptible to persistent HCV infection when supported in an in vitro culture by stromal elements1 may allow significant advances in in vitro modeling of HCV biology. Despite such recent advances in in vitro options for the study of hepatotropic viruses, in vitro cell culture systems do not Mitomycin C solubility dmso necessarily recapitulate in vivo cell differentiation and function or virus-cell interactions in the infected host. Progress in the in vivo study of hepatotropic viruses
has been constrained by the narrow host range of HBV and HCV. Productive infection by HBV and HCV is limited to humans and chimpanzees, and although important advances in this field
have been made by analyses of infected chimpanzees, sizable studies are limited by ethical considerations, high cost, and limitations on availability. Studies of the Pekin duck and woodchuck models have led to advances in our understanding of hepadnaviruses; however, we are hampered by the outbred nature of these models and by a lack of available data on the immunobiology of these hosts and the restricted availability of suitable reagents. Attempts to develop small animal Resveratrol models for HCV have been impeded somewhat by similar limitations, and attempts to infect primates other than chimpanzees with HCV have not been successful. The development of HBV transgenic mice has been critical in revealing the mechanisms of control of HBV replication,2 but although transgenic animals produce infectious virus, murine hepatocytes are not susceptible to HBV infection. Largely because of the restricted tropism of HBV and HCV, attempts to develop small animal models for the study of human hepatotropic virus have recently centered on the creation of human liver chimeric immunodeficient mice. The first developed and best characterized of these systems is the one based on transgenic mice expressing urokinase plasminogen activator (uPA) in hepatocytes under the albumin promoter (Alb-uPA mice).