Because Bid serves to amplify the death response, it is not universally required for apoptosis induction. In some cell types, known as type I cells, caspase-8 activation results in direct, Bidindependent activation of the apoptosis effectors, caspase-3 and caspase-7 [29] . In others, known as type II cells, apoptosis requires amplification of death signals through stimulation of the mitochondrial pathway. In these cases, Bid serves to link the extrinsic and intrinsic apoptotic pathways [30] . Since the requirement for Bid in reovirus virulence is dependent on viral dose, we think that the role of Bid as an apoptosis regulator contributes to viral replication and consequent neurovirulence. Thus, we hypothesize that neurons function like type I cells when infected at a higher dose of virus and do not require the amplification of the mitochondrial apoptotic pathway via Bid to undergo apoptotic cell death. However, at lower infectious doses, neurons function like type II cells and require Bid-driven activation of the intrinsic mitochondrial apoptotic cascade to elicit cell death. This model also may explain why primary neuronal cultures infected with reovirus at a high MOI do not appear to require cytochrome c release and caspase-9 activation for apoptosis induction [42] .