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:
- Swine Influenza Virus Introduction in Pig Farms: A Semi-Quantitative Risk Assessment in Northern Italy 1 days ago
- Molecular Characterization of Highly Pathogenic Avian Influenza H5N1 Viruses Circulating in Bulgaria During 2024–2025: Evidence for Hidden Circulation and Zoonotic Risk Markers 1 days ago
- Dissecting Cell Death Pathways in Influenza A Virus Infection: Comparative Insights from Human Models 1 days ago
- Clinical and Laboratory Findings in Cats with Confirmed Avian Influenza A/H5N1 Virus Infection During the 2023 Outbreak in Poland: A Retrospective Case Series of 22 Cats 1 days ago
- Concentration- and Time-Dependent Virucidal Responses of Major Transboundary Animal Disease Viruses to Disinfectants 1 days ago
[Go Top] [Close Window]


