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 cour
se of the disease and the poor prognosis for long-term persistent infection
make this pathogen a serious medical and socioeconomical problem. The iden
tification of the viral genome similar to 10 years ago rapidly led to the d
elineation of the genomic organization and the structural and biochemical c
haracterization of several virus proteins. However, studies of the viral li
fe 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 hig
hly efficient cell culture model could be developed. This system is based o
n the self replication of engineered HCV minigenomes (replicons) in a trans
fected 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. (C) 2001 Elsevier Science B.V. All rights reserved.