FIG. 6.

Anti-HCV effects of inhibitors of the sphingolipid biosynthetic pathway. Subgenomic replicon cells derived from HCV isolate N or JFH-1, as well as HCVcc-producing cells, were treated with ISP-1 (0.1, 1, or 10 μM), HPA-12 (0.1, 1, or 10 μM) or alpha interferon (IFN) (100 U/ml) for 72 h. HCV RNA titers in the replicon cells (A) and the HCV core protein content of the culture medium of infected cells (C) were determined. Data are means from four independent experiments. Error bars, standard deviations. (B) De novo synthesis of sphingolipid in the absence or presence of ISP-1 (10 μM) and HPA-12 (10 μM) was monitored in duplicate by metabolic labeling with [¹⁴C]serine for 2 h at 37°C. Cer, ceramide; PE, phosphatidylethanolamine; PS, phosphatidylserine.