Reovirus Activates a Caspase-Independent Cell Death Pathway

Berger, Angela K.; Danthi, Pranav

Steps following escape from the endosome but prior to viral RNA and protein synthesis are required for initiation of the apoptotic pathway (19) . This induction process involves the IB kinase (IKK)-mediated activation of the classical form of the transcription factor NF-B, comprised of RelA and p50 subunits (20, 21) . Activation of NF-B early following infection is required for the cleavage of the BH3-only member of the Bcl-2 family of mitochondrial proteins, Bid, via the initiator caspase, caspase-8 (14, 22) . The cleaved form of Bid, truncated Bid (tBid), amplifies the apoptotic signal through the mitochondria to activate the initiator caspase, caspase-9 (23) (24) (25) . These events result in activation of the effector caspase, caspase-3, and culminate in cell death. In addition, the protein kinase JNK (c-Jun N-terminal kinase), the cytosolic cysteine protease calpain, and the transcription factor IRF-3 have been shown to contribute to efficient induction of apoptosis by reovirus (26) (27) (28) (29) . It remains unknown if components of the signaling cascade described above are required for reovirusinduced cell death in all cell types.