1887

Journal of General Virology

Volume 91, Issue 6

The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1 Free

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 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.

  • Received:
  • Accepted:
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2010-06-01
2021-01-28
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The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1
J. Gen. Virol. 91, 1439 (2010); https://doi.org/10.1099/vir.0.018465-0
/content/journal/jgv/10.1099/vir.0.018465-0
/content/journal/jgv/10.1099/vir.0.018465-0
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