Novel cell culture systems for the hepatitis C virus

Infections with the hepatitis C virus (HCV) are a major cause of acute and chronic liver disease. The high prevalence of the virus, the insidious course of the disease and the poor prognosis for long-term persistent infection make this pathogen a serious medical and socioeconomical problem. The identification of the viral genome approximately 10 years ago rapidly led to the delineation of the genomic organization and the structural and biochemical characterization of several virus proteins. However, studies of the viral life cycle as well as the development of antiviral drugs have been difficult because of the lack of a robust and reliable cell culture system. Numerous attempts have been undertaken in the past few years but only recently a highly efficient cell culture model could be developed. This system is based on the self replication of engineered HCV minigenomes (replicons) in a transfected human hepatoma cell line. A summary of the various HCV cell culture models with a focus on the replicon system and its use for drug development is described.