Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin.

ABSTRACT: We have carried out a comprehensive analysis of the determinants of human influenza A H3 hemagglutinin evolution. We consider three distinct predictors of evolutionary variation at individual sites: solvent accessibility (as a proxy for protein fold stability and/or conservation), Immune Epitope Database (IEDB) epitope sites (as a proxy for host immune bias), and proximity to the receptor-binding region (as a proxy for one of the functions of hemagglutinin-to bind sialic acid). Individually, these quantities explain approximately 15% of the variation in site-wise dN/dS. In combination, solvent accessibility and proximity explain 32% of the variation in dN/dS; incorporating IEDB epitope sites into the model adds only an additional 2 percentage points. Thus, while solvent accessibility and p

SUBMITTER: Meyer AG 

PROVIDER: S-EPMC4447415 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature