Establishment of Replication-Competent HCV Strain with Minimum Modifications

The HCV cell culture system, consisting of the JFH-1 strain and HuH-7 cells, has been broadly used to assess the complete HCV life cycle in cultured cells. However, being able to use multiple HCV strains in such a system is vital for future studies of this virus. We recently established a novel HCV cell culture system using another HCV genotype 2a strain, J6CF, which replicates in chimpanzees but not in cultured cells. We identified effective cell culture-adaptive mutations and established a replication-competent J6CF strain with minimum modifications in cultured cells. The strategy of how we established the replication-competent HCV strain and how we identified the effective cell culture-adaptive mutations is described here and could prove useful for establishing other replication-competent HCV strains.