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

Richard, A; Tulasne, D

When a viral infection threatens cells, one of the first measures they take is to induce apoptosis to restrict viral replication and spread. [1] [2] [3] Dying this way, host cells are likely to generate specific signals aiming at triggering the immune system with innate and/or adaptative responses allowing the eradication of the invader. 4, 5 On the other hand, viruses have evolved a huge arsenal of strategies meant to either counteract or deal with this destructive process to ensure their survival. [6] [7] [8] Apoptotic cell death is accompanied by characteristic morphological changes (cellular rounding-up and volume reduction, chromatin condensation, nuclear fragmentation, plasma membrane blebbingy) and at a molecular level by the activation of first initiator and then effector cysteinyl aspartate proteinases or caspases. 9,10 Activated caspases act through a catalytic Cys that hydrolyzes peptide bonds within the substrate, with a stringent specificity for Asp residue at P1 position (the nature of residues at positions P2, P3 and P4 depending on the caspase). Caspase substrates include a large number and variety of cellular proteins that participate through their cleavage to the strong apoptosisrelated morphological changes, as well as other physiological processes. Interestingly, viral proteins are also likely to be cleaved by caspases but until 2004, only four of them were reported as such and suggested as advantaging the associated viruses through their cleavage. 11 Since, their number has greatly increased and at least 16 viruses are now known to express proteins that undergo caspase cleavage. Here, we aim at updating these cleavages and discussing their biological relevance. From apoptosis inhibition to the improvement or attenuation of viral amplification, caspase cleavage of VPs highlights a potential new fascinating viral strategy to handle apoptosis induction.