Since the SREBP signaling pathway is induced by HCVencoded proteins during infection [19, [30] [31] [32] , we tested the effect of inhibiting this pathway on the HCV lifecycle in human hepatoma cells. Huh-7.5.1 cells were treated with increasing moi (1-50) of Ad-Spn4A.RRLL(r), Ad-Spn4A.RRLL(s), or Ad-Empty (control) for 48 hours in complete media with or without exogenously added sterols followed by 72 hours of infection with HCV. The number of HCV-infected cells, as evidenced by positive core protein expression, was measured using Cellomics HCS ( Figure 5A ). It was determined that Spn4A.RRLL(s) expression inhibited HCV infection in a dose-dependent manner compared to control-treated cells. HCV infection was not significantly reduced in cells infected with Ad-Spn4A.RRLL(s) at a moi of 1. A moi of 12.5, however, caused a 40% reduction, a moi of 25 caused a 60% reduction, and a moi of 50 caused a 75% reduction in the number of HCV-infected cells compared to controls. Spn4A.RRLL(r) had no significant impact on HCV infection up to adenovirus moi 50 when compared to the control ( Figure 5A ). Supplementing sterol and lipid metabolites significantly restored infectivity when cells were treated with moi 50 of Ad-Spn4A.RRLL(s), where a 2-fold increase in HCV infection compared to non-supplemented cells was observed ( Figure 5A ). These results show that the anti-HCV activity of Spn4A.RRLL(s) is, at least in part, associated with its capacity to decrease intracellular lipid stores within the host cells.