FIG. 10.

Model of vaccinia virus-mediated apoptosis inhibition. Fas initiated apoptosis occurs via activation of caspase 8 and by the subsequent proteolytic cleavage of Bid. Once cleaved, Bid translocates to the mitochondria, resulting in a loss of the inner-mitochondrial-membrane permeability transition and the release of cytochrome c. The release of cytochrome c (Cyto. c) results in activation of caspase 9 via interaction with the adapter molecule Apaf1 and the subsequent activation of caspase 3. Additionally, loss of the inner-membrane permeability transition can be triggered by staurosoporine and atractyloside. Vaccinia virus infection manipulates this pathway at two separate points. First, the vaccinia virus-encoded serine protease inhibitor SPI-2/crmA inhibits the activity of caspase 8. Second, vaccinia virus infection also inhibits apoptosis by modulating the PT pore, thereby preventing the loss of cytochrome c and activation of caspase 9.