To determine whether these differences in neurological injury are attributable to alterations in tropism of reovirus in the absence of Bid, sections of mouse brain were stained for reovirus antigen. Reovirus displayed similar tissue distribution in wild-type and Biddeficient mouse brains, indicating that Bid expression does not influence reovirus tropism (data not shown). The CA3 region of a wild-type mouse brain showed reovirus antigen in areas coincident with extensive neuronal damage ( Figure 7B ). Regions positive for reovirus antigen also stained with an antibody for activated caspase-3. Although similar regions of Bid-deficient mouse brains contained reovirus antigen, staining was of diminished intensity and frequency ( Figure 7B) , consistent with the decreased efficiency of reovirus replication in the CNS ( Figure 6B) . Accordingly, few cells showing intense caspase-3 staining were observed in regions that contained reovirus. These data suggest that neuronal apoptosis following reovirus infection is diminished in the absence of Bid. Thus, Bid links reovirus replication and apoptosis induction in the production of fatal encephalitis.