Structural Basis for a Novel Interaction between the NS1 Protein Derived from the 1918 Influenza Virus and RIG-I

Structure. 2015 Nov 3;23(11):2001-10. doi: 10.1016/j.str.2015.08.007. Epub 2015 Sep 10.

Abstract

The influenza non-structural protein 1 (NS1) plays a critical role in antagonizing the innate immune response to infection. One interaction that facilitates this function is between NS1 and RIG-I, one of the main sensors of influenza virus infection. While NS1 and RIG-I are known to interact, it is currently unclear whether this interaction is direct or if it is mediated by other biomolecules. Here we demonstrate a direct, strain-dependent interaction between the NS1 RNA binding domain (NS1(RBD)) of the influenza A/Brevig Mission/1918 H1N1 (1918(H1N1)) virus and the second caspase activation and recruitment domain of RIG-I. Solving the solution structure of the 1918(H1N1) NS1(RBD) revealed features in a functionally novel region that may facilitate the observed interaction. The biophysical and structural data herein suggest a possible mechanism by which strain-specific differences in NS1 modulate influenza virulence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / chemistry*
  • DEAD-box RNA Helicases / metabolism
  • Humans
  • Influenza A Virus, H1N1 Subtype / chemistry
  • Influenza Pandemic, 1918-1919
  • Molecular Docking Simulation*
  • Molecular Sequence Data
  • Protein Binding
  • Receptors, Immunologic
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / metabolism

Substances

  • INS1 protein, influenza virus
  • Receptors, Immunologic
  • Viral Nonstructural Proteins
  • RIGI protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases