Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis

Richard, A; Tulasne, D

Baculoviruses are invertebrate viruses that encode several antiapoptotic products including IAPs, P49 and P35. When lacking P35, the baculovirus prototype Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) induces apoptosis and fails to replicate, whereas P35 rescue inhibits cell death and restores viral replication. 12 Interestingly, P35 is proteolytically cleaved on infection 13, 14 and the 84 DQMD 87 k cleavage site is required for P35-mediated apoptosis suppression. P35 directly inhibits many caspases, including insect Sf-caspase 1, human caspases 1, 3, 6, 7, 8 and 10 and mouse caspase 1. 14,15 Indeed, P35 cleavage products remain irreversibly associated to the caspase through a covalent thioester bond between P35 D87 residue and the caspase catalytic cysteine. 16, 17 Although being 50%-related to P35, P49 yet exhibits a different caspase cleavage site ( 91 TVTD 94 k) that confers to P49 its antiapoptotic properties. 18 Caspase suppression by P49 also involves its cleavage by and stable association to the targeted caspases although acting as a dimer. 19 Besides effector caspases, P49 also affects initiator caspases that P35 fails to suppress, like insect Sf-caspase X and human initiator caspase 9.