Reovirus infection of HEK293 epithelial cells leads to a biphasic loss of full-length (FL) Bid [16] . Since a mitochondrial amplification loop through Bid is required for apoptosis only in some cell types, such as hepatocytes [29, 30] , it is not known if Bid is cleaved in all cell types infected by reovirus. In addition, although calpains [31, 32] , caspases [26, 33, 34, 35] , and cathepsins [36, 37, 38, 39] can mediate Bid cleavage and have been implicated in apoptosis induction by reovirus [15, 16, 40] , the precise identity of the protease that generates tBid following reovirus infection is not known. To determine whether tBid is generated following reovirus infection of fibroblasts, and to define the mechanism of Bid cleavage following reovirus infection, we infected murine L929 fibroblasts with reovirus strain type 3 Dearing (T3D) and monitored levels of FL Bid and tBid over 48 h ( Figure 1A ). While levels of FL Bid remained unchanged in mock-infected cells, we observed loss of FL Bid between 24 and 48 h post-infection. Decreased levels of FL Bid correlated with a corresponding increase in levels of tBid. To determine whether the generation of tBid results in activation of the mitochondrial loop of the intrinsic apoptotic pathway, we assessed