We report for the first time a new RNA replication system with a hepatitis C virus (HCV) strain (AHI) derived from a patient with acute hepatitis C. Using an HCV replicon RNA library constructed with the AH1 strain (genotype 1b), we first established a cloned cell line, sAH1, harboring the HCV replicon. Cured cells obtained with interferon treatment of sAH1 cells were used for transfection with genome-length HCV RNA possessing four mutations found in sAH1 replicon. Consequently, one cloned cell line, AH1, supporting efficient replication of genome-length HCV RNA was obtained. By the comparison of AH1 cells with the O cells supporting genome-length HCV RNA (HCV-O strain) replication, we found different anti-HCV profiles of interferon-gamma and cyclosporine A between AH1 and O cells. Reporter assay analysis suggests that the diverse effects of interferon-gamma are due to the difference in HCV strains, but not the cellular environment. (c) 2008 Elsevier Inc. All rights reserved