Figure 5

NS5A L31 and Y93 polymorphism associated with DCV resistance. (a) DCV-induced polymorphism on NS5A L31 in the HCV GT2a strain JFH1. Illumina MiSEQ sequencing analysis was carried out using total RNA from HCV-infected Huh7 xenografts, which were recovered from the indicated mice receiving saline, DCV, or HA1077 plus DCV for 27 days. sm, silent mutation. (b) Mutation frequency on various L31 substitutions in mice with HCV rebound or with undetectable serum HCV titers after administration of DCV or DCV plus HA1077 for 27 days. ND, not detected. Asterisks indicate the residues that show a significant increase or decrease in mutation frequency. *P < 0.05 by unpaired two-tailed Student’s t-test. (c) L31 polymorphism in mice receiving HA1077 for 15 days. (d) Y93 polymorphism was analyzed as in (a).