PPARα knockdown reverses the IFN enhancing effect of WY-14643. JFH1-infected Huh-7 cells were transfected with PPARα siRNA, or scrambled RNA control. Cells were pretreated with WY-14643 for 24 h, or mock treated, then treated with 0.5 U/mL IFN-α. Treatment of Huh-7 cells with PPARα siRNA significantly reduced PPARα expression at baseline, 24 and 48 h by ∼85%, 80%, and 75%, respectively (A). In cells transfected with scrambled RNA, WY-14643 maintained its IFN-α enhancing activity and reduced JFH1 replication, compared with mock-treated cells (B). PPARα siRNA knockdown prevented the effect of WY-14643, with no significant reduction in HCV RNA. Graphs demonstrate an average of 3 experimental replicates (*P<0.05, **P<0.01).