The identification of an essential role for Bid in apoptosis induction following reovirus infection allowed us to examine the relationship between NF-kB activation and Bid cleavage. To determine whether Bid is required for activation of NF-kB following reovirus infection, we compared reovirus-induced NF-kB activation in wild-type and Bid-deficient cells using a reporter assay. Wild-type and Bid-deficient MEFs were transfected with an NF-kB-luciferase reporter plasmid and infected with reovirus. Analogous to treatment with TNFa, a control NF-kB agonist, reovirus infection resulted in equivalent (,2-to 3-fold) activation of NF-kB-driven gene expression in wild-type and Bid-deficient cells ( Figure 3A ). These results indicate that Bid is dispensable for NF-kB activation following reovirus infection and suggest that either reovirus-induced NF-kB activation occurs prior to Bid cleavage or that NF-kB activation and Bid cleavage occur in parallel but independent pathways that both function in apoptosis induction by reovirus.