The present inventors used the previously developed H77/JFH 1.sub.T27OOC,A4O8OT (1a/2a), J4/JFH .sub.1T2996C,A4827T,.DELTA.HVRI (1b/2a), J6/JFH .sub.1.DELTA.HVRI (2a/2a), J8/JFH 1.sub..DELTA.HVRI (2b/2a), S52/JFH 1.sub.T27i8G,.tau.7i6oc (3a/2a), SA13/JFH 1.sub.C34O5G,A3696G (5a/2a) and HK6a/JFH 1T.sub.1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH 1 (genotype 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis of the viruses identified mutations adapting H77/JFH 1.sub.T27OOC,A4O8OT,.DELTA.HVR1 (1a/2a), J8/JFH .sub.1.DELTA.HVR1 (2b/2a), S52/JFH 1.sub.T2718G,T716OC,.DELTA.HVR1 (3a/2a) and J4/JFH 1.sub.T2996C,A4827T,.DELTA.HVR1 (1b/2a) to the HVR1 deletion.