title: Caspase-3-like proteases are activated by infection but are not required for replication of vesicular stomatitis virus.
abstract: Infection with vesicular stomatitis virus (VSV), the prototype rhabdovirus, causes apoptotic DNA fragmentation, but the role of apoptosis in the VSV-host interaction remains unclear. Apoptosis is the gene-regulated mechanism triggered by a wide variety of stimuli that lead to cell death in a choreographed manner. In the present study, infection of the Jurkat T cell line with VSV led to activation of caspase-3 and caspase-7, with subsequent apoptotic events involving poly (ADP ribose) polymerase (PARP) cleavage, DNA fragmentation, and membrane damage. Caspase activation was correlated with viral protein expression suggesting a link between viral replication and apoptosis. We hypothesized that VSV replication might depend on apoptosis and that the inhibition of apoptosis would lead to significant decreases in viral titers. When various inhibitors of apoptosis in VSV-infected cells were used, 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 apoptosis but not in vitro viral replication. Apoptosis following VSV infection is likely to be either a host-cell attempt to control viral replication or may be a ploy used by the virus to facilitate its in vivo replication and spread.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, 702 Barnhill Dr., Riley Hospital Rm. 0615, Indianapolis, IN 46202-5200, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Hobbs
authors.forename: R H
authors.initials: RH
authors.lastname: Schloemer
authors.forename: G
authors.initials: G
authors.lastname: Hommel-Berrey
authors.forename: Z
authors.initials: Z
authors.lastname: Brahmi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism*; D053938:DNA Fragmentation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D009842:Oligopeptides / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000472:pathogenicity / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D004792:Enzyme Precursors; D009842:Oligopeptides; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases