Baculovirus inhibitors of apoptosis (IAPs) block activation of Sf-caspase-1

We have investigated if ability of Sf-caspase-1 end two mammalian caspases, caspase-1 and caspase-3, to induce apoptosis in Spodoptera frugiperda Sf-21 insect cells, While the transient expression of the pro-Sf-caspase-1 did not induce apoptosis, expression of the pro-domain deleted form, p31, or coexpression of the two subunits of mature Sf-caspase-1, p19 and p12, induced apoptosis in Sf-21 cells. The behavior of Sf-caspase-1 resembled that of the closely related mammalian caspase, caspase-3, and contrasted with that of the mammalian caspase-1, the pro-form of which was active iii inducing apoptosis in Sf-21 cells. The baculovirus caspase inhibitor P3S blocked apoptosis induced by active forms of all three caspases. In contrast, members of the baculovirus inhibitor of apoptosis (IAP) family failed to block active caspase-induced apoptosis, However, during viral infection, expression of OpIAP or CpIAP blocked the activation of pro-Sf-caspase-1 and the associated induction of apoptosis, Thus, the mechanism bu which baculovirus IAPs inhibit apoptosis is distinct from the mechanism by which P35 blacks apoptosis and involves inhibition of the activation of pro-caspases like Sf-caspase-1.