To determine whether reovirus-induced cleavage of Bid is dependent on signaling via TRAIL-R, we monitored Bid cleavage following infection of TRAIL-R-deficient cells ( Figure 4D ). At 48 h post-infection of wild-type cells with T3D, FL Bid was cleaved to generate tBid. In contrast, FL Bid was not cleaved in T3D-infected TRAIL-R-deficient cells. While the apparent difference in the levels of FL Bid in wild-type and TRAIL-Rdeficient cells was not reproducible, we consistently observed that levels of FL Bid remained unchanged in TRAIL-R-deficient cells following reovirus infection. These data indicate that TRAIL-R contributes to the induction of apoptosis by reovirus and suggest that cleavage of Bid following reovirus infection is dependent on TRAIL-R signaling.