Interaction of the Influenza A Virus NS1 Protein with the 5'-m7G-mRNA·eIF4E·eIF4G1 Complex

The influenza A virus (IAV) is responsible for seasonal epidemics that result in hundreds of thousands of deaths worldwide annually. The non-structural protein 1 (NS1) of the IAV inflicts various antagonistic processes on the host during infection. These processes include inhibition of the host interferon system, inhibition of the apoptotic response, and enhancement of viral mRNA translation, all of which contribute to the overall virulence of the IAV. Although the mechanism by which NS1 stimulates translation is unknown, NS1 has been shown to bind both poly-A binding Protein 1 and eukaryotic initiation factor 4 gamma 1 (eIF4G1), two proteins necessary for cap-dependent translation. We directly analyzed the interaction between NS1 and eIF4G1 within the context of the 5'-m⁷G-mRNA·eIF4E·eIF4G1 complex. Interestingly, our studies show that NS1 can bind this complex in the presence or absence of 5'-m⁷G-mRNA. Additionally, we were interested in investigating whether NS1 interacts with eIF4E directly. Our results indicate that NS1 can bind to eIF4E only in the absence of 5'-m⁷G-mRNA. Considering previous data, we propose that NS1 stimulates translation by binding to eIF4G1 and recruiting the 43S pre-translation initiation complex to the mRNA.