Intra-patient neuraminidase mutations in avian H5N1 influenza virus reduce sialidase activity to complement weaker hemagglutinin binding and facilitate human infection.

ABSTRACT: Clade 2.2 H5N1 influenza viruses have caused an unusually high number of human infections, providing a unique opportunity to investigate early molecular steps associated with host adaptation. Although most work has focused on hemagglutinin (HA), the contribution of neuraminidase (NA) to these early adaptive events has remained unclear. By analyzing publicly available sequences from clade 2.2-infected patients, we identified 20 NA mutations and compared their phenotypes to 20 mutations acquired during diversification in primary human airway cells under drug-free conditions. Most patient-derived NA mutations resulted in modest reductions in sialidase activity, keeping activity within a functional range that supported improved replication in α2,6 sialylglycan (α2,6 Sia)-dominant environments,

SUBMITTER: Watanabe Y 

PROVIDER: S-EPMC12829795 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature