Reovirus-induced apoptosis is mediated by TRAIL

Members of the tumor necrosis factor (TNF) receptor superfamily and their a ctivating ligands transmit apoptotic signals in a variety of systems. We no w show that the binding of TNF-related, apoptosis-inducing ligand (TRAIL) t o its cellular receptors DR5 (TRAILR2) and DR4 (TRAILR1) mediates reovirus- induced apoptosis. Anti-TRAIL antibody and soluble TRAIL receptors block re ovirus-induced apoptosis by preventing TRAIL-receptor binding. In addition, reovirus induces both TRAIL release and an increase in the expression of D R5 and DR4 in infected cells. Reovirus-induced apoptosis is also blocked fo llowing inhibition of the death receptor-associated, apoptosis-inducing mol ecules FADD (for LAS-associated death domain) and caspase 8. We propose tha t reovirus infection promotes apoptosis via the expression of DR5 and the r elease of TRAIL from infected cells. Virus-induced regulation of the TRAIL apoptotic pathway defines a novel mechanism for virus-induced apoptosis.