Caspase-3-like proteases are activated by infection but are not required for replication of vesicular stomatitis virus

Infection with vesicular stomatitis virus (VSV), the prototype rhabdovirus, causes apoptotic DNA fragmentation. but the role of apoptosis in the VSV-h ost interaction remains unclear. Apoptosis is the gene-regulated mechanism triggered by a wide variety of stimuli that lead to cell death in a choreog raphed manner. In the present study, infection of the Jurkat T cell line wi th VSV led to activation of caspase-3 and caspase-7, with subsequent apopto tic events involving poly (ADP ribose) polymerase (PARP) cleavage, DNA frag mentation, and membrane damage. Caspase activation was correlated with vira l protein expression suggesting a link between viral replication and apopto sis. We hypothesized that VSV replication might depend on apoptosis and tha t the inhibition of apoptosis would lead to significant decreases in viral titers. When various inhibitors of apoptosis in VSV-infected cells were use d, PARP cleavage and DNA fragmentation were inhibited but the production of infectious progeny was not affected. In addition, we demonstrated that the activation of caspase-3-like proteases is required for VSV-induced apoptos is but not in vitro viral replication. Apoptosis following VSV infection is likely to be either a host-cell attempt to control viral replication or ma y be a ploy used by the virus to facilitate its in vivo replication and spr ead. (C) 2001 Elsevier Science B.V. All rights reserved.