Structure-Guided Functional Annotation of the Influenza A Virus NS1 Protein Reveals Dynamic Evolution of the p85β-Binding Site during Circulation in Humans.

ABSTRACT: Rational characterization of virulence and host-adaptive markers in the multifunctional influenza A virus NS1 protein is hindered by a lack of comprehensive knowledge about NS1-host protein protein interfaces. Here, we surveyed the impact of amino acid variation in NS1 at its structurally defined binding site for host p85β, a regulator of phosphoinositide 3-kinase (PI3K) signaling. Structure-guided alanine scanning of all viral residues at this interface defined 10 positions contributing to the interaction, with residues 89, 95, 98, 133, 145, and 162 being the most important. A bioinformatic study of >24,000 publicly available NS1 sequences derived from viruses infecting different hosts highlighted several prevalent amino acid variants at the p85β interface that either enhanced (I95) or we

SUBMITTER: Lopes AM 

PROVIDER: S-EPMC5640874 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature