Novel Permissive Cell Lines for Complete Propagation of Hepatitis C Virus

Hepatitis C virus (HCV) is a major etiologic agent of chronic liver diseases. Although the HCV life cycle has been clarified by studying laboratory strains of HCV derived from the genotype 2a JFH-1 strain (cell culture-adaptedHCV [HCVcc]), themecha-nisms of particle formation have not been elucidated. Recently, we showed that exogenous expression of a liver-specificmicroRNA, miR-122, in nonhepatic cell lines facilitates efficient replication but not particle production of HCVcc, suggesting that liver-spe-cific host factors are required for infectious particle formation. In this study, we screened human cancer cell lines for expression of the liver-specific-fetoprotein by using a cDNA array database and identified liver-derived JHH-4 cells and stomach-derived FU97 cells, which express liver-specific host factors comparable to Huh7 cells. These cell lines permit not only replication of HCV RNA but also particle formation upon infection with HCVcc, suggesting that hepatic differentiation participates in the ex-pression of liver-specific host factors required for HCV propagation. HCV inhibitors targeting host and viral factors exhibited different antiviral efficacies between Huh7 and FU97 cells. Furthermore, FU97 cells exhibited higher susceptibility for propaga-tion of HCVcc derived from the JFH-2 strain than Huh7 cells. These results suggest that hepatic differentiation participates in the expression of liver-specific host factors required for complete propagation of HCV. IMPORTANCE Previous studies have shown that liver-specific host factors are required for efficient replication of HCV RNA and formation o