Figure 5: Viral IDPP resistance study and generation of IDPP-susceptible HCV genotype 1 variant.

(A) IDPP-resistant HCV was created by culturing of JFH1-GFP virus-infected Huh-7.5 cells with increasing compound concentrations (2-fold) as indicated. (B) Three mutations in glycoprotein E1 were identified and are indicted by asterisks ‘*’ (upper). Resistance to IDPP was evaluated with recombinant viruses (lower). (C) DRC analysis with IDPP-recombinant viruses including the given amino acid substitutions. (D) Supernatant transfer assay with parental (wtJFH1) and IDPP-recombinant virus (recJFH1/E1G257R). (E) Generation of IDPP-susceptible genotype 1 virus (TN) by amino acid substitution (Q257G) in HCV E1 glycoprotein. At 72 h p.i., intracellular HCV RNA levels were determined by qRT-PCR. Relative HCV RNA levels normalized to GAPDH are shown.