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

Richard, A; Tulasne, D

Rather similarly, the product of the orf390 gene expressed by the crustacean-infecting white spot syndrome virus (WSSV) was also shown to exert antiapoptotic properties. Insect cells SF9 stably expressing orf390 gene strongly resist both viral-and actinomycin D-induced apoptosis. 20 Like P35 and P49, ORF390 (also referred as WSSV449 or AAP-1) is suggested to act as an inhibitor substrate 21 and is able to block several caspases, including human caspases 3 and 9 as well as insect Sf-caspase 1 in vitro. ORF390 ability to suppress caspase activity is associated with consensual caspase cleavage sites: 269 DEVD 272 k that targets caspase 3, and 230 VETD 233 k and 300 LEHD 303 k that are both required for caspase 9 inhibition. Although each site specifically targets one protease, the three of them are needed to reach maximal caspase inactivation. 20 For baculoviruses and WSSV, inhibiting apoptosis is crucial to achieve their life cycle. These different invertebrateinfecting viruses encode proteins exhibiting active caspase cleavage sites, just as cellular substrates do, but with the special ability to irreversibly freeze the protease activity. This leads to a very potent and broad caspase inhibition, which keeps the host cell machinery available and fit for viral amplification.