Figure 4

RO8191 activates a novel IFN-like pathway.

(a–e) The inhibition of HCV replicon replications by each agent is shown (mean and SD). The HCV replicon cells were transfected with 50 nM of the indicated siRNAs (blue, red and yellow bars). (a, b) The anti-HCV replicon activity of RO8191 was reduced by knockdown of JAK1 (a) but not Tyk2 (b). Forty-eight hours after transfection, the HCV replicon cells were treated with 1.5 μM RO8191 or 3 IU/mL IFN-α. Twenty-four hours after treatment with each agent, the replication levels of HCV RNA were analyzed using a luciferase assay. (c–e) The anti-HCV replicon activity of RO8191 was reduced by knockdowns of STAT2 (d) and IRF9 (e), but not STAT1 (c). Forty-eight hours after transfection, the HCV replicon cells were treated with 1.5 μM RO8191, 3 IU/mL IFN-α, or 50 ng/mL IFN-γ. Twenty-four hours after treatment, the replication levels of HCV RNA were analyzed using a luciferase assay. (f) A schematic showing the pathways of RO8191 and IFN-α. The data were statistically analyzed using Student’s t-test and differences were considered significant at p values < 0.05.