Old dog, new tricks: Influenza A virus NS1 and in vitro fibrillogenesis

The influenza NS1 protein is involved in suppression of the host immune response. Recently, there is growing evidence that prion-like protein aggregation plays an important role in cellular signaling and immune responses. In this work, we obtained a recombinant, influenza A NS1 protein and showed that it is able to form amyloid-like fibrils in vitro. Using proteolysis and subsequent mass spectrometry, we showed that regions resistant to protease hydrolysis highly differ between the native NS1 form (NS1-N) and fibrillar form (NS1-F); this indicates that significant structural changes occur during fibril formation. We also found a protein fragment that is capable of inducing the process of fibrillogenesis at 37 °C. The discovery of the ability of NS1 to form amyloid-like fibrils may be relevant to uncovering relationships between influenza A infection and modulation of the immune response. •Recombinant NS1 protein is capable of forming amyloid-like fibrils.•Native form NS1 features a protease-resistant fragment from a.a. residues 1 to 78.•The fibrillar NS1 form's C-terminus is hydrolyzed by trypsin least of all.•During fibril formation, SDS-resistant non-native dimers form.•The NS1 Beta domain likely plays an important role in conformational transition.