To determine whether cleavage-induced Bid activation is dependent on NF-kB, we examined Bid cleavage in cells lacking p65/RelA, an NF-kB subunit required for apoptosis induction following reovirus infection [8] . Infection of wild-type MEFs with reovirus results in generation of tBid at 36-48 h after infection ( Figure 3B ). In contrast, infection of p65/RelA-deficient MEFs with reovirus did not lead to tBid generation even though efficient viral replication is observed in these cells [8] . Treatment of both wild-type and p65/RelA-deficient MEFs with apoptotic agonists TNFa and cycloheximide resulted in efficient cleavage of Bid, indicating that cell-death pathways leading to Bid cleavage are intact in both cell types. These findings suggest that cleavage and activation of Bid following reovirus infection requires NF-kB and place Bid cleavage subsequent to NF-kB signaling in response to reovirus infection. Moreover, since Bid amplifies death responses from the extrinsic apoptosis pathway by activating the mitochondrial loop, these findings suggest that death-receptor signaling during reovirus infection occurs in an NF-kB-dependent manner.