Signaling via the intrinsic pathway is essential for reovirusinduced apoptosis [16] . This observation, along with the dependence of mitochondrial apoptotic signaling on cleavage of Bid, suggests that Bid serves an essential function in reovirusinduced apoptosis. To directly test whether Bid is required for apoptosis induction following reovirus infection, we compared reovirus-induced apoptosis in wild-type and Bid-deficient MEFs. For these experiments, MEFs were infected with T3D, and apoptosis was assessed by chemiluminescent measurement of the activity of caspase-3 and caspase-7, which serve as effector caspases for both the extrinsic and intrinsic apoptotic pathways ( Figure 2A ). In comparison to mock-infected cells, infection of wild-type cells resulted in a significant increase in caspase-3/7 activity at 24 h post-infection. Since MEFs are poorly permissive for reovirus infection [41] , staining of infected cells by indirect immunofluorescence indicated that adsorption with 100 PFU/cell of T3D resulted in infection of only ,8% of cells at 20 h post infection (data not shown). Despite a low frequency of infection, this MOI resulted in an ,3-fold increase in caspase-3/7 activity. When infection was initiated at 1000 PFU/cell, ,20% cells were infected (data not shown), and caspase-3/7 activity increased ,5fold. In contrast, infection of Bid-deficient cells resulted in minimal caspase-3/7 activity following infection at either MOI. Increase in caspase-3/7 activity following treatment of each cell type with a broad-spectrum protein kinase inhibitor, staurosporine, was equivalent (,5-fold), demonstrating that although Bid-deficient cells possess functional death-signaling pathways, they resist apoptosis induction by reovirus.