UC San Diego

The annual epidemics caused by the influenza A virus causes hundreds of thousands of deaths worldwide. The non-structural protein of the influenza A virus, NS1, is the main antagonist of the host immune response which assists in the proliferation and virulence of the virus. NS1 is important for preventing nuclear export of host mRNA into the cytoplasm, avoiding activation of the viral RNA sensor RIG-I and the stimulation of mRNA translation. Despite being extensively studied, NS1’s ability to influence the host’s translational machinery is not yet understood. However, previous studies have shown NS1 is able to interact with the eukaryotic translation initiation factor 4G (eIF4G) and poly(A)-binding protein 1 (PABP1), two proteins crucial to the translation initiation process. Here we directly measured the NS1 and eIF4G interaction in the context of the 5'-m7G-mRNA•eIF4E•eIF4G1 complex. Our results indicate NS1 is able to bind this complex both in the presence and absence of 5'-m7G-mRNA. Similarly, our experiment show NS1 can bind eIF4E but only in the absence of 5'-m7G-mRNA. In conjunction with previously reported data detailing NS1’s ability to bind the 40S ribosomal subunit, we hypothesize NS1 stimulates translation by facilitating the interaction between the 5'-m7G-mRNA•eIF4E•eIF4G1 complex and 40S-containing pre-translation initiation complex through a network of interactions.