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Journal of Virology, April 2008, p. 3796-3802, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02020-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Early Phosphatidylinositol 3-Kinase/Akt Pathway Activation Limits Poliovirus-Induced JNK-Mediated Cell Death{triangledown}

Arnaud Autret, Sandra Martin-Latil, Cynthia Brisac, Laurence Mousson, Florence Colbère-Garapin, and Bruno Blondel*

Biologie des Virus Entériques, Institut Pasteur, 75724 Paris cedex 15, France

Received 13 September 2007/ Accepted 11 January 2008

Poliovirus (PV)-induced apoptosis seems to play a major role in tissue injury in the central nervous system (CNS). We have previously shown that this process involves PV-induced Bax-dependent mitochondrial dysfunction mediated by early JNK activation in IMR5 neuroblastoma cells. We showed here that PV simultaneously activates the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway in these cells, limiting the extent of JNK activation and thereby cell death. JNK inhibition is associated with PI3K-dependent negative regulation of the apoptosis signal-regulating kinase 1, which acts upstream from JNK in PV-infected IMR5 cells. In poliomyelitis, this survival pathway may limit the spread of PV-induced damage in the CNS.

* Corresponding author. Mailing address: Biologie des Virus Entériques, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France. Phone: (33) 1.40.61.35.90. Fax: (33) 1.40.61.34.21. E-mail: bblondel{at}pasteur.fr

{triangledown} Published ahead of print on 23 January 2008.

Journal of Virology, April 2008, p. 3796-3802, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02020-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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