Smith VA, Schall AR, Tomsho JW. Nonstructural Protein 1 of Influenza A (NS1A) Demonstrates Strain-Specific dsRNA Binding Capabilities. ACS Infect Dis. 2025 Mar 13
Nonstructural protein 1 of influenza A (NS1A) is a key virulence factor produced inside host cells infected with Influenza A Virus (IAV) and consists of an N-terminal dsRNA binding domain (RBD) and a C-terminal effector domain (ED), joined by a flexible linker. While NS1A is a highly promiscuous protein with a number of intracellular functions, its primary function is nonspecific dsRNA binding that enables influenza to evade our innate immune system. For this reason, NS1A has long been proposed as a potential drug target. Previous research in the field has demonstrated the necessity of dimer formation through the RBD to enable dsRNA binding, which is further enhanced by oligomerization through ED interactions. However, there has been minimal exploration of potential strain-specific effects on dsRNA binding. Most existing studies are limited to the A/Udorn/307/1972 strain, often with a C-terminal tail deletion. Here we utilize fluorescence polarization (FP) paired with fluorescence-based electrophoretic mobility shift assays (fEMSA) to characterize the dsRNA binding properties of NS1A from the H1N1 strain responsible for the 1918 "Spanish Flu" with an intact C-terminal tail. We show that A/Brevig Mission/1/1918 NS1A contains specific residues in the RBD that enhance dsRNA binding. We further demonstrate that both Brevig Mission and Udorn NS1A bind directly to dsRNA through the highly basic C-terminal tail of the ED. These novel binding interactions may have contributed to the increased pathogenicity of the 1918 flu pandemic and may have implications for NS1A-targeted antivirals.
See Also:
Latest articles in those days:
- Extended influenza seasons in Australia and New Zealand in 2025 due to the emergence of influenza A(H3N2) subclade K viruses 6 hours ago
- Dynamic ensemble deep learning with multi-source data for robust influenza forecasting in Yangzhou 6 hours ago
- Structural and immunological characterization of the H3 influenza hemagglutinin during antigenic drift 6 hours ago
- Novel Highly Pathogenic Avian Influenza A(H5N1) Virus, Argentina, 2025 9 hours ago
- Avian influenza overview September - November 2025 1 days ago
[Go Top] [Close Window]


