Evaluation on the receptor-binding preference and drug resistance of H9N2 influenza viruses

Abstract

The enzootic and zoonotic nature of H9N2 avian influenza viruses pose a persistent threat to global poultry industry and human health. This particular subtype influenza virus raises public concerns because it possesses human receptor specificity. In this study, four H9N2 virus strains clustered into the G57-like viruses preferentially bound to SAα2,6 receptors as demonstrated in the results from the receptor-binding assay. The molecular dynamic simulation showed that HAQ226L substitution of H9N2 viruses may alter the conformation of the 220-loop of hemagglutinin (HA) and thus optimize the contacts between HA and human receptors, thereby increasing the preference for α2,6-linkages. The acquisition of an additional N-glycosylation site at position 264 close to the enzyme active sites of neuraminidase of H9N2 viruses induced the loss of hydrogen bonding between 276E at the enzyme active sites and Zanamivir and further led to occurrence of Zanamivir-resistant of viruses. This study shows the relationship between the conformational changes due to amino acid variations and viral biological phenotypes, which emphasizes the necessity for monitoring the continual evolution of H9N2 viruses and comprehensively assessing their potential zoonotic threat.