Belinostat-resistant TCL cells are hypersensitive to oncolytic reovirus replication and Reolysin-mediated cell death. (A) Reovirus viral load is significantly greater in belinostat-resistant TCL cells. Karpas-299 and HuT-78 cells were treated for 48 hours with 45 and 90 PFUs of Reolysin per cell, respectively. Reovirus accumulation was visualized by electron microscopy (arrows indicate reovirus accumulation). (B) Quantification of reovirus in parental and belinostat-resistant TCL cells. The number of reovirus particles per cell was quantified using ImageJ software. Data are shown as mean ± SD (n = 5). *P < .05 indicates a significant difference compared with parental cells treated with Reolysin. (C) Belinostat-resistant cells are hypersensitive to Reolysin-mediated cell death. Belinostat-resistant and parental cells were treated with the indicated amounts of Reolysin, and cell viability was determined by MTT assay after 72 hours of treatment. Data are shown as mean ± SD (n = 3). *P < .05 indicates a significant difference compared with parental cells treated with the same concentration of Reolysin. (D) Belinostat-resistant cells display increased sensitivity to Reolysin-mediated apoptosis. TCL cells were treated with Reolysin for 48 hours, and apoptosis was quantified by PI-FACS analysis in parental and belinostat-resistant Karpas-299 and HuT-78 cells. Data are shown as mean ± SD (n = 3). *P < .05 indicates a significant difference compared with parental cells.