[Bluetongue virus infection: signaling pathway activated during apoptosis].
Bluetongue (BTV) is a double-stranded RNA virus that induces apoptosis both in mammalian cell cultures and in target tissues. To elucidate the apoptosis pathways in BTV infection, we have examined in detail the apoptosis mechanism by examination of caspases, Bax, cytochrome c, Smac/DIABLO and NF-B signalling pathways. In this report, after cell infection with BTV, the activation of caspase 8 was detected, proving the extrinsic receptor binding apoptotic pathway. Apoptosis followed a sequential pathway involving the detection of activated Bcl-2 family members. Furthermore, its translocation to the mitochondria, as well as the release of cytochrome c and Smac/Diablo confirmed that BTV apoptosis involves the sequential intrinsic pathway. In addition, we demonstrated that NF-kappaB was activated following BTV infection and cell treatment with an inhibitor peptide before BTV infection, prevented NF-kappaB activation and substantially reduced cellular apoptosis. Our accumulating data concerning the activation of Bax, cytochrome c, Smac/DIABLO and NF-kappaB clarify the mechanism of apoptosis during BTV infection, and confer a better understanding of the primary role of apoptosis in BTV pathogenesis.
Mortola
E
E
Inmunología Veterinaria, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118, (1900) La Plata, Argentina. mortola@fcv.unlp.edu.ar
Larsen
A
A
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001820:Bluetongue virus / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D004789:Enzyme Activation; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D045304:Cytochromes c; D020169:Caspases