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.
Structured evidence records
Evidence records
2 total
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.95
Key finding
The Q226H mutation in avian H5N1 hemagglutinin enables binding to human-type α2-6 sialic acid receptors, representing a structural adaptation towards human infection.
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.
Method
cryo-EM | receptor-binding assays
Study design
structural analysis
Transmission direction
molecular mechanism only
Event type
receptor-binding site mutation enabling human-type receptor recognition
A human case in British Columbia was identified with infection by a clade 2.3.4.4b H5 avian influenza virus containing a mixture of 226Q/H in hemagglutinin.
