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 underwent chromatin condensation and DNA fragmentation within 48 h post-infection. An increased level of the apoptotic enhancer, Bax, was detected within 24 h after infection. In contrast to Bax, the production of the apoptotic antagonist, Bcl-2, remained unchanged. Shortly after detection of Bax, caspase 1 (ICE) was upregulated. Reduction of DNA fragmentation in rabies virus infected cultures pretreated with YVAD and DEVD suggested that more than one subfamily of caspase functioned in the death process. Significant degradation of the DNA repair enzyme, poly ADP-ribose polymerase (PARP), was revealed after caspase upregulation. This study showed that replication of rabies viruses in mouse neuroblastoma cells induced the Bax-related death program leading to destruction of the DNA repair system probably by caspase activity.
Ubol
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S
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. scsul@mucc.mahodol.ac.th
Sukwattanapan
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C
Utaisincharoen
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P
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000833:Animals, Suckling; D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D051379:Mice; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D011820:Rabies virus / Q000254:growth & development* / Q000472:pathogenicity; D014779:Virus Replication; D051028:bcl-2-Associated X Protein
D000590:Amino Acid Chloromethyl Ketones; C494827:Bax protein, mouse; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D020169:Caspases; D020170:Caspase 1