Autret Arnaud, Martin-Latil Sandra, Brisac Cynthia, Mousson Laurence, Colbère-Garapin Florence, Blondel Bruno
Biologie des Virus Entériques, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris cedex 15, France.
J Virol. 2008 Apr;82(7):3796-802. doi: 10.1128/JVI.02020-07. Epub 2008 Jan 23.
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.
脊髓灰质炎病毒（PV）诱导的细胞凋亡似乎在中枢神经系统（CNS）的组织损伤中起主要作用。我们之前已经表明，这一过程涉及PV诱导的由IMR5神经母细胞瘤细胞中早期JNK激活介导的Bax依赖性线粒体功能障碍。我们在此表明，PV在这些细胞中同时激活磷脂酰肌醇3激酶（PI3K）/Akt生存信号通路，限制JNK激活的程度，从而限制细胞死亡。JNK抑制与凋亡信号调节激酶1的PI3K依赖性负调控相关，凋亡信号调节激酶1在PV感染的IMR5细胞中位于JNK的上游起作用。在脊髓灰质炎中，这种生存途径可能会限制PV诱导的损伤在中枢神经系统中的扩散。
