Study on sequence- Structure - function variation and correnlated mutations of hemagglutinin of influenza a virus

Abstract

Hemagglutinin (HA) plays an important role in host immune evasion across influenza virus evolution process. The correlation between HA sequence, structure and function has yet fully investigated. In this study, by combining of sequence variability, structural motifs, functional stability and statistical analysis on conserved epitopic/binding sites, we identified potential therapeutic features of HA that would be valuable in broad spectrum Influenza A vaccine design. We were able to recognize not only common motifs but also distinct ones across 18 IAV HA subtypes. Using correlated sequence evolution, we additionally identified co-evolved mutations associated with maintaining HA structural and functional stability. Particularly, we found 4 highly conserved epitopic regions with one of those showed large exposed surface area and no coevolving residues. Our study provides an important insight for rational design and identification of novel therapeutics targeting universally recognized feature of Influenza A virus (IAV) HA. Keywords: Hemagglutinin (HA), influenza A virus (IAV), multiple sequence alignment, consensus sequence, phylogenetic tree, correlated mutation. 1. INTRODUCTION