Prevalence and mechanisms of evolutionary contingency in human influenza H3N2 neuraminidase.

ABSTRACT: Neuraminidase (NA) of human influenza H3N2 virus has evolved rapidly and been accumulating mutations for more than half-century. However, biophysical constraints that govern the evolutionary trajectories of NA remain largely elusive. Here, we show that among 70 natural mutations that are present in the NA of a recent human H3N2 strain, >10% are deleterious for an ancestral strain. By mapping the permissive mutations using combinatorial mutagenesis and next-generation sequencing, an extensive epistatic network is revealed. Biophysical and structural analyses further demonstrate that certain epistatic interactions can be explained by non-additive stability effect, which in turn modulates membrane trafficking and enzymatic activity of NA. Additionally, our results suggest that other biophysic

SUBMITTER: Lei R 

PROVIDER: S-EPMC9616408 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature