Recently, it has been reported that nuclear factor like 2 is a master transcriptional activator of an array of genes for metabolisms as well as genes for cytoprotection, detoxification and antioxidation, in complex with v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog. Thus, finally, we investigated involvement of the Nrf2/Maf complex in the metabolic CCT128930 alteration in the HCV-persistently infected cells. Nonetheless, we observed two minor surges of core production with slight increase in the ratio of HCV-positive cells and hypothesized that the cells at the surges contain cells that are resistant to death and permissive for HCV persistent infection. In order to isolate such a cell clone, we attempted limiting dilutions using the cells at the 2nd surge. We performed this procedure three times consecutively to purify a clone, C3, C3-6 and finally C3-6-15 cell. We considered the C3-6-15 cell as an HCV-persistently infected cell line and designated it as ��HPI cell�� because 100% of the cells were infected with HCV and they has supported HCV for 609 days. It was shown that HCVcc from lytic infection with JFH-1 contains two types of HCV particles: low-density particles with high infectivity and high-density particles with low infectivity. A similar result was obtained by sedimentation analysis of HCVcc from HPI cells, suggesting that infectious HCVcc might be associated with the lipoproteins, similar to lytic infection. Then, to explore the HCV genomic variations that might have occurred in the process of the establishment, we sequenced the RT-PCR products for HCV in the culture medium of HPI cells at passage 7 and found that deduced amino acid substitutions were frequent in the E1, E2, and NS5A regions. Since the supernatant from the cultured HPI cells NPS-2143 induced cell lysis when used to inoculate na?ve Huh7.5 cells, we speculated that the persistence of HCV depended not on such HCV genomic variations, but on cellular factor of HPI cells. To verify this, we cured HPI cells with cyclosporine, and designated the resulting cells as ‘CuHPI’. Expectedly, these cells were susceptible to HCVcc but permissive for HCV persistency for at least 120 days.