Identification of thermostability-enhancing mutations in H9N2 avian influenza virus hemagglutinin

H9N2 avian influenza viruses pose a persistent threat to poultry production and human health, demanding improved control strategies. This study addresses a key knowledge gap by uncovering the molecular determinants that modulate the stability of the hemagglutinin (HA) protein in H9N2 viruses. We identify specific HA mutations that increase thermostability, a property potentially linked to environmental persistence. Furthermore, our findings demonstrate a critical interplay between HA stability and essential viral functions, including receptor binding, hemagglutination activity, replication kinetics, and overall acid tolerance. By disentangling these properties, we provide insights into the mechanisms underlying HA-mediated viral entry and infectivity, which could inform the development of more effective vaccines and therapeutics.