It is not known how Bid controls the efficiency of reovirus replication in the CNS. One possibility is that Bid-regulated apoptosis is required for efficient release of virus from neurons. Therefore, cell-to-cell spread of reovirus within the CNS may be inefficient in the absence of Bid. As an extension of this idea, blockade of apoptosis by other means also should cause a delay in reovirus replication. However, although symptoms of encephalitis are alleviated in NF-kB p50-deficient mice or in wild-type mice treated with a JNK inhibitor due to a reduction in virus-induced neuronal apoptosis, reovirus replication kinetics are not substantially diminished [11, 12] . Consistent with these findings, diminished virulence of apoptosis-defective reovirus mutants is not accompanied by significant decreases in reovirus replication efficiency in the CNS [4, 7] . Apoptosis following reovirus infection can occur in absence of p50, albeit at low efficiency [8] . Similarly, apoptosisdefective reovirus mutants retain some capacity to induce apoptotic cell death [4, 7] . Therefore, it is possible that in comparison to reovirus infection of Bid-deficient mice, CNS apoptosis was incompletely blocked in these other studies. Such a difference in the efficiency of apoptosis inhibition could explain the observed discrepancy in the requirement for Bid and other host or viral modulators of apoptosis for efficient replication of reovirus. A second possibility is that a Bid function not related to its capacity to regulate apoptosis contributes to reovirus replication in the CNS.