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

Richard, A; Tulasne, D

Viruses Face Up to Apoptosis: Die Harder. There are clear evidences concerning the relevance of viral protein caspase cleavages in the physiology of viruses ( Figure 1) . Coherently, such a modification is used to directly fight apoptosis and AcMNPV as well as WSSV express proteins acting as strong and broad inhibitor caspase substrates. For other viruses, caspase cleavage probably allows the removal of specific regions that reveals or eliminates functional domains or signals. In some cases, this leads to full viral amplification (AMDV NS1, HPV E1), with the striking example of AMDV NS1 protein that needs to be cleaved by caspases to translocate to the nucleus and eventually exert its functions. On the contrary, caspase cleavage can result in the attenuation of the virus by generating new viral products acting as dominant negatives of NS proteins (H-1PV NS1, KSHV ORF57) or unfit for virus packaging when structural proteins are concerned (AMDV VP and possibly FCV capsid protein). Interestingly, such attenuation at a cellular level might hold importance regarding the possibility for viruses to establish permissive and/or persistent infection at a higher scale (i.e. multicellular organisms). The functional consequences of some viral protein caspase cleavages still remain debated or elusive because of the difficulty of investigating hazardous entities (influenza, HCV), the multitude of strains and genotypes (influenza, HCV, adenovirus) or the lack of appropriate tools such as cellular or animal models allowing to recapitulate the viral life cycle (TGEV, MCV). When caspase cleavages of viral proteins work in too mysterious ways, it is sometimes concluded that they constitute a mechanism of degradation resulting from the host fighting back the infection. However, the caspase-related products detected are mostly stable, suggesting they could be somehow involved in the viral life cycle as mentioned right above. Besides, knowing how high the mutation rates of viruses can be, 50 or that some viral oncoproteins (like v-Rel) adapted to resist caspase cleavage through evolution unlike their cellular counterparts, 51 keeping caspase cleavage sites seems very unlikely if viruses do not somehow profit from them. As caspase cleavage of viral proteins occurs in all sorts of proteins (structural or non-structural) and in all sorts of viruses (DNA as well as RNA), this suggests that it constitutes a strong strategy to handle apoptosis. By managing to use the molecular effectors of apoptosis to protect themselves from eradication without any additional genetic information required, viruses prove once again how fascinating their adaptability can be.