Fig 8.

Effects of the caspase inhibitors on apoptosis induced by DCPE and KSHV replication induced by treatment with DCPE. The effects of increasing concentrations of the general caspase inhibitor Z-VAD-FMK, the caspase-9 inhibitor Ac-LEHD-CHO, the caspase-6 and caspase-8 inhibitor Ac-VEID-CHO, and the caspase-3 inhibitor Ac-AAVALLPAVLLALLAPDGVD-CHO on cell apoptosis, as measured by flow cytometric assays for Annexin V and propidium iodide and the production of KSHV virions as protected KSHV DNA. Control treatments included cells not treated with any inducer (Untreated), in which the cells were treated with DMSO, the vehicle used to dissolve DCPE, or cells treated with TPA (as a positive control for the induction of viral replication). Four-component Gompertz plots were fitted to the dose-response data (Stata 11), except for the data obtained when the cells were treated with the caspase-6 inhibitor Ac-VEID-CHO, since no activity was observed for this inhibitor. The general Z-VAD-FMK and specific caspase-9 and caspase-3 inhibitors had similar dose-response curves for inhibition of apoptosis and viral replication. Inhibition of the end effector caspase-3 appears to be sufficient to block KSHV replication triggered in association with apoptosis.