Chapter 2 Cell Culture Systems for Hepatitis C Virus

Due to the obligatory intracellular life style of viruses, cell culture systems for efficient viral propagation are crucial to obtain a detailed understanding of the virus host cell interaction. For hepatitis C virus (HCV) the development of permissive and authentic culture models has been and continues to be a challenging task. The first ef­ forts to culture HCV had limited success and range back to before the virus was molecularly cloned in 1989. Since then several major breakthroughs have gradually overcome limitations in culturing the virus and sequentially permitted analysis of viral RNA replication, cell entry and ultimately the complete replication cycle in cultured cells in 2005. Until today, basic and applied HCV research greatly benefit from these tremendous efforts which spurred multiple com­ plementary cell based model systems for distinct steps of the HCV replication cycle. When used in combination they now permit deep insights into the fascinating biology of HCV and its interplay with the host cell. In fact drug development has been much facilitated and our understanding of the molecular determinants of HCV replication has grown in parallel to these advances. Building on this ground­ work and further refining our cellular models to better mimic the ar­ chitecture, polarization and differentiation of natural hepatocytes should reveal novel unique aspects of HCV replication. Ultimately, models to culture primary HCV isolates across all genotypes may teach us important new lessons about viral functional adaptations that have evolved in exchange with its human host and that may ex­ plain the variable natural course of hepatitis C.