Early phosphatidylinositol 3-kinase/Akt pathway activation limits poliovirus-induced JNK-mediated cell death.

Arnaud Autret (1) , Sandra Martin-Latil (1) , Cynthia Brisac (1) , Laurence Mousson (1) , Florence Colbère-Garapin (1) , Bruno Blondel (1)

1 BVE - Biologie des Virus entériques

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.

Domaines: Virologie

Arnaud Autret, Sandra Martin-Latil, Cynthia Brisac, Laurence Mousson, Florence Colbère-Garapin, et al.. Early phosphatidylinositol 3-kinase/Akt pathway activation limits poliovirus-induced JNK-mediated cell death.. Journal of Virology, 2008, 82 (7), pp.3796-802. ⟨10.1128/JVI.02020-07⟩. ⟨pasteur-00316053⟩