Apoptosis is frequently induced to inhibit virus replication during infection of 
Enterovirus 71 (EV71). On the contrary, anti-apoptotic pathway, such as PI3K/Akt 
pathway, is simultaneously exploited by EV71 to accomplish the viral life cycle. 
The relationship by which EV71-induced apoptosis and PI3K/Akt signaling pathway 
remains to be elucidated. In this study, we demonstrated that EV71 infection 
altered Bax conformation and triggered its redistribution from the cytosol to 
mitochondria in RD cells. Subsequently, cytochrome c was released from 
mitochondria to cytosol. We also found that c-Jun NH2-terminal kinase (JNK) was 
activated during EV71 infection. The JNK specific inhibitor significantly 
inhibited Bax activation and cytochrome c release, suggesting that EV71-induced 
apoptosis was involved into a JNK-dependent manner. Meanwhile, EV71-induced Akt 
phosphorylation involved a PI3K-dependent mechanism. Inhibition of the PI3K/Akt 
pathway enhanced JNK phosphorylation and the JNK-mediated apoptosis upon EV71 
infection. Moreover, PI3K/Akt pathway phosphorylated apoptosis signal-regulating 
kinase 1 (ASK1) and negatively regulated the ASK1 activity. Knockdown of ASK1 
significantly decreased JNK phosphorylation, which implied that ASK1 
phosphorylation by Akt inhibited ASK1-mediated JNK activation. Collectively, 
these data reveal that activation of the PI3K/Akt pathway limits JNK-mediated 
apoptosis by phosphorylating and inactivating ASK1 during EV71 infection.