Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus.
Avian coronavirus infectious bronchitis virus (IBV) is the causative agent of chicken infectious bronchitis, an acute, highly contagious viral respiratory disease. Replication of IBV in Vero cells causes extensive cytopathic effects (CPE), leading to destruction of the entire monolayer and the death of infected cells. In this study, we investigated the cell death processes during acute IBV infection and the underlying mechanisms. The results show that both necrosis and apoptosis may contribute to the death of infected cells in lytic IBV infection. Caspase-dependent apoptosis, as characterized by chromosomal condensation, DNA fragmentation, caspase-3 activation, and poly(ADP-ribose) polymerase degradation, was detected in IBV-infected Vero cells. Addition of the general caspase inhibitor z-VAD-FMK to the culture media showed inhibition of the hallmarks of apoptosis and increase of the release of virus to the culture media at 16 h postinfection. However, neither the necrotic process nor the productive replication of IBV in Vero cells was severely affected by the inhibition of apoptosis. Screening of 11 IBV-encoded proteins suggested that a 58-kDa mature cleavage product could induce apoptotic changes in cells transiently expressing the protein. This study adds one more example to the growing list of animal viruses that induce apoptosis during their replication cycles.
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Institute of Molecular Agrobiology, 1 Research Link, The National University of Singapore, Singapore 117406, Singapore. liudx@ima.org.sg
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D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000032:analysis / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002875:Chromosomes / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D005057:Eukaryotic Cells; D001351:Infectious bronchitis virus / Q000378:metabolism / Q000472:pathogenicity*; D008970:Molecular Weight; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D014764:Viral Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D020169:Caspases