Infection with the hepatitis C virus (HCV) is a major cause of chronic live
r disease. HCV is an enveloped plus-strand RNA virus closely related to fla
vi- and pestiviruses. The first cloning of the HCV genome, about 10 years a
go, initiated research efforts leading to the elucidation of the genomic or
ganization and the definition of the functions of most viral proteins. Desp
ite this progress the lack of convenient animal models and appropriate in v
itro propagation systems have hampered a full understanding of the way the
virus multiplies. This review summarizes our current knowledge about HCV re
plication and describes attempts pursued in the last few years to establish
efficient and reliable cell culture systems.