The present inventors used the previously developed H77/JFH1T27OOC,A4O8OT (1a/2a), J4/JFH1T2996C,A4827T,ΔHVRI (1b/2a), J6/JFH1ΔHVRI (2a/2a), J8/JFH1ΔHVRI (2b/2a), S52/JFH1T27i8G,τ7i6oc (3a/2a), SA13/JFH1C34O5G,A3696G (5a/2a) and HK6a/JFH1T1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH1 (geno-type 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/JFH1T27OOC,A4O8OT,ΔHVR1 (1a/2a), J8/JFH1ΔHVR1 (2b/2a), S52/JFH1T2718G,T716OC,ΔHVR1 (3a/2a) and J4/JFH1T2996C,A4827T,ΔHVR1 (1b/2a) to the HVR1 deletion.