RABIES VIRUS-REPLICATION INDUCES BAX-RELATED, CASPASE DEPENDENT APOPTOSIS IN MOUSE NEUROBLASTOMA-CELLS

Rabies virus has been shown to induce apoptosis in infected cells? but the intracellular pathway of cell killing is unknown. In this report, we show that rabies virus infected mouse neuroblastoma cells underwen t chromatin condensation and DNA fragmentation within 48 h post-infect ion. An increased level of the apoptotic enhancer, Bar, was detected w ithin 24 h after infection. In contrast to Bar, the production of the apoptotic antagonist, Bcl-2, remained unchanged. Shortly after detecti on of Bar, caspase 1 (ICE) was upregulated. Reduction of DNA fragmenta tion in rabies virus infected cultures pretreated with YVAD and DEVD s uggested that more than one subfamily of caspase functioned in the dea th process. Significant degradation of the DNA repair enzyme, poly ADP -ribose polymerase (PARP), was revealed after caspase upregulation. Th is study showed that replication of rabies viruses in mouse neuroblast oma cells induced the Bar-related death program leading to destruction of the DNA repair system probably by caspase activity. (C) 1998 Elsev ier Science B.V. All rights reserved.