tetano
Editor, Senior Moderator
bioRxiv
[Preprint]. 2026 May 26:2026.05.21.726965.
doi: 10.64898/2026.05.21.726965.
The Q226H Mutation in Avian H5N1 Hemagglutinin Mediates a Path towards Structural Adaptation in Humans
Ross A Edwards, Oluwafemi F Adu, Egor P Tchesnokov, Dana Kocincova, Emma Woolner, Zoe Turner, Duong T Bui, Lara K Mahal, Nathan Zelyas, John S Klassen, Andrei P Drabovich, Kalyan Das, Matthias Götte
The global outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) among birds and the spillover to mammals increases the risk for humans. A recent case in British Columbia with a clade 2.3.4.4b H5 virus infection revealed a mixture of 226Q/H in the receptor-binding site of hemagglutinin. While significant changes in pre-existing immunity by H1 or H3 polyclonal sera are not evident, we show that the Q226H mutation enables binding to human-type a2-6 sialic acid receptors. High-resolution cryo-EM structures provide a basis for the alteration in receptor preference and show that a possible path towards human adaptation also requires a conformational change of the bound a2-6-sialylated glycan. Continued surveillance for additional mutations that could enhance this phenotype is warranted.
[Preprint]. 2026 May 26:2026.05.21.726965.
doi: 10.64898/2026.05.21.726965.
The Q226H Mutation in Avian H5N1 Hemagglutinin Mediates a Path towards Structural Adaptation in Humans
Ross A Edwards, Oluwafemi F Adu, Egor P Tchesnokov, Dana Kocincova, Emma Woolner, Zoe Turner, Duong T Bui, Lara K Mahal, Nathan Zelyas, John S Klassen, Andrei P Drabovich, Kalyan Das, Matthias Götte
- PMID: 42244705
- PMCID: PMC13232203
- DOI: 10.64898/2026.05.21.726965
The global outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) among birds and the spillover to mammals increases the risk for humans. A recent case in British Columbia with a clade 2.3.4.4b H5 virus infection revealed a mixture of 226Q/H in the receptor-binding site of hemagglutinin. While significant changes in pre-existing immunity by H1 or H3 polyclonal sera are not evident, we show that the Q226H mutation enables binding to human-type a2-6 sialic acid receptors. High-resolution cryo-EM structures provide a basis for the alteration in receptor preference and show that a possible path towards human adaptation also requires a conformational change of the bound a2-6-sialylated glycan. Continued surveillance for additional mutations that could enhance this phenotype is warranted.