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Poliovirus induces Bax-dependent cell death mediated by c-Jun NH2-terminal kinase.

Abstract : Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome c release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member of the Bcl-2 family; this activation involves its conformational change and its redistribution from the cytosol to mitochondria. Neutralization of Bax by vMIA protein expression prevents cytochrome c release, consistent with a contribution of PV-induced Bax activation to mitochondrial outer membrane permeabilization. Interestingly, we also found that c-Jun NH(2)-terminal kinase (JNK) is activated soon after PV infection and that the PV-cell receptor interaction alone is sufficient to induce JNK activation. Moreover, the pharmacological inhibition of JNK by SP600125 inhibits Bax activation and cytochrome c release. This is, to our knowledge, the first demonstration of JNK-mediated Bax-dependent apoptosis in PV-infected cells. Our findings contribute to our understanding of poliomyelitis pathogenesis at the cellular level.
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Submitted on : Friday, October 31, 2008 - 7:23:22 PM
Last modification on : Monday, January 13, 2020 - 5:08:09 PM
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Arnaud Autret, Sandra Martin-Latil, Laurence Mousson, Aurélie Wirotius, Frédéric Petit, et al.. Poliovirus induces Bax-dependent cell death mediated by c-Jun NH2-terminal kinase.. Journal of Virology, American Society for Microbiology, 2007, 81 (14), pp.7504-16. ⟨10.1128/JVI.02690-06⟩. ⟨pasteur-00166062⟩

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