INFECTION AND REPLICATION OF NATURALLY OCCURRING HEPATITIS C VIRUS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatitis C virus (HCV) infection afflicts about 170 million individuals worldwide. However, the HCV life cycle is partially understood because it has not been possible to infect human hepatocytes in culture. The current Huh-7 systems use cloned, synthetic HCV RNA expressed in hepatocellular carcinoma cells to produce pseudo particles, but these cells cannot be infected with naturally occurring HCV obtained from infected patients. Here, we describe a human hepatocyte culture permissible to the infection with naturally occurring HCV genotypes 1, 2, 3 and 4 in the blood of HCV-infected patients. The culture system mimics the biology and kinetics of HCV infection in humans, and produces infectious virions that can infect na¿ve human hepatocytes. This culture system should complement the existing systems, and may facilitate the understanding of the HCV life cycle, it effects in the natural host cell, the hepatocyte, as well as the development of novel therapeutics and vaccines.