The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1
Lu, Xinya and Masic, Aleksandar and Li, Yang and Shin, YeunKyung and Liu, Qiang and Zhou, Yan,, 91, 1439-1449 (2010),
doi = https://doi.org/10.1099/vir.0.018465-0,
publicationName = Microbiology Society,
issn = 0022-1317,
abstract= It has previously been reported that influenza A virus infection activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, it has been shown that the mutant influenza A virus PR8-SH3-mf-1, which is unable to activate the PI3K/Akt pathway, is more pro-apoptotic than the wild-type (WT) virus. However, the molecular pathways involved in regulating this process remain unknown. Here, it is reported that, although both WT and PR8-SH3-mf-1 viruses induced apoptosis, the PR8-SH3-mf-1 virus consistently showed greater potential to induce mitochondrial membrane disruption, cytochrome c release, and translocation and conformational change of Bax than the WT virus. Furthermore, the PR8-SH3-mf-1 virus was unable to phosphorylate apoptosis signal-regulating kinase 1 (ASK1) but induced higher levels of c-jun N-terminal kinase (JNK) phosphorylation than the WT virus. Blocking JNK activity could inhibit virus-induced Bax activation and apoptosis. These results reveal that, during influenza A virus infection, the PI3K/Akt pathway negatively regulates the JNK pathway via ASK1, thereby inhibiting JNK-dependent, Bax-mediated apoptosis.,
language=,
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