Characterization of coxsackievirus B3-caused apoptosis under in vitro conditions.
Among several mechanisms of pathogenesis of the frequent and sometimes serious infections with coxsackievirus B3 (CVB3), one detail is apoptosis. Recently, a new apoptotic mechanism involving the specific interaction between the capsid protein VP2 of the highly virulent variant CVB3H3 and the proapoptotic host protein Siva was identified. The relevance of this observation for virus pathogenicity was shown in a BALB/c mouse model using CVB3H3 and the interaction-deficient mutant virus CVB3H310A1. In this study these results were verified and extended under in vitro conditions. The different apoptotic capability of CVB3H3 versus CVB3H310A1 was demonstrated by apoptotic nuclear condensation, DNA fragmentation, expression of Siva mRNA, and caspase-3 activation. The virus-specific differences were caused by the VP2 capsid proteins, which was shown by overexpression of the single VP2H3 and VP2H310A1 protein. Furthermore, the involvement of apoptosis in virus progeny production and the associated appearance of the cytopathic effect was demonstrated by application of the pan-caspase inhibitor Z-VAD-FMK. These in vitro results indicate that the induction of apoptosis during CVB3H3 infection is based on the interaction between the capsid protein VP2 and the proapoptotic protein Siva, independently from the complex situation in vivo.
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D053938:DNA Fragmentation; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology* / Q000821:virology*; D051379:Mice; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C106549:SIVA1 protein, human; C484569:Siva protein, mouse; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases