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

Richard, A; Tulasne, D

As described above, AMDV NS1 protein is cleaved by caspases, which allows full viral replication. Interestingly, AMDV capsid proteins VP1 and 2 are also processed by caspases on viral infection or ectopic expression. 31 The cleavage generates a stable 26-kDa product, VPx, and can be partly prevented by the pharmacological inhibition of caspases 6, 8, 9 and 10, and completely by a pan caspase inhibitor. Besides, VP protein expression in either transfected or AMDV-infected cells mainly activates caspase 10, followed by caspases 6, 9, 3 and 7, with caspase 7 as the more efficient in VP cleavage in vitro. Altogether, these data argue for the involvement of several caspases in VP cleavage. AMDV-G strain grows more efficiently at 31.8 1C than 37 1C. The alteration of the caspase site within AMDV-G increases both VP and genomic copies production at the non-optimal temperature of 37 1C and shows no significant effects at 31.8 1C, suggesting that VP caspase cleavage attenuates AMDV-G life cycle. In vivo AMDV-G infection might thus be regulated by active caspases because it only occurs at 37 1C. Interestingly, NS1 cleavage favors viral DNA replication while VP processing would limit the packaging of progeny virions. As it is possible that both NS1 and VP cleavages do not inevitably occur simultaneously depending on the pattern of activated caspases, it would result in either effective or attenuated viral replication and allow the virus to spread or persist.