SH3 Binding Motif 1 in Influenza A Virus NS1 Protein Is Essential for PI3K/Akt Signaling Pathway Activation

Abstract

Recent studies have demonstrated that influenza

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

“…In a previous report, we showed that WT virus led to caspase-9 phosphorylation, whereas PR8-SH3-mf-1 virus did not (Shin et al, 2007a). Taking our data together, we propose the following model of how the PI3K/Akt pathway regulates apoptosis during influenza A virus infection (Fig.…”

“…We previously reported that mutant virus PR8-SH3-mf-1 carrying three mutations (P162A/P164A/ P167A) in NS1 failed to induce PI3K/Akt activity but induced more severe apoptosis than the WT virus (Shin et al, 2007a). The current study was initiated to define how the PI3K/Akt pathway regulates influenza A virus-induced apoptosis.…”

“…Influenza A virus-induced apoptosis (Shin et al, 2007a). This prompted us to investigate whether the mitochondrial pathway was involved in influenza A virus-induced apoptosis.…”

“…Because remarkable morphological differences have been observed between cells infected with PR8-SH3-mf-1 relative to the WT virus [influenza A/PR/8/34 (PR8)] at 16 h post-infection (p.i.) (Shin et al, 2007a), we compared the kinetics of the apoptosis induced by WT and PR8-SH3-mf-1 virus within 12-16 h p.i. A549 cells were infected by the viruses at an m.o.i.…”

“…Studies using equine influenza virus have shown that influenza virus infection induces apoptosis via a c-jun N-terminal kinase (JNK) or stress-activated protein kinase cascade (Lin et al, 2001). containing P162A/P164A/P167A mutations in NS1, was unable to activate the PI3K/Akt pathway and induced more severe apoptosis than the wild-type (WT) virus (Shin et al, 2007a), suggesting that the PI3K/Akt pathway functions to suppress virus-induced apoptosis. The current study was initiated to identify the molecular mechanisms underlying influenza virus-induced apoptosis.…”