OmniVira

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
PMID42244705 DOI10.64898/2026.05.21.726965 Year2026 Journal bioRxiv : the preprint server for biology bioRxiv Languageeng Statusepublish

Abstract

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.

Supporting text Virus Host Location

Evidence records

3 total
Functional Mechanism
3 records · 2 evidence types
Evidence type Receptor Usage
1 records
OVE11259 Receptor Usage
Key finding

The Q226H mutation in HPAI A(H5N1) hemagglutinin enables binding to human-type α2-6 sialic acid receptors, indicating altered receptor usage toward human receptor specificity.

Virus
Influenza A virus H5N1
Host
human Homo sapiens Experimental system
Location
Not specified
Supporting text

we show that the Q226H mutation enables binding to human-type a2-6 sialic acid receptors.

Method
binding assay | cryo-EM structure analysis
Receptors
human-type α2-6 sialic acid receptor
Evidence type Molecular Adaptation
2 records
OVE11260 Molecular Adaptation
Key finding

Cryo-EM structures of HPAI A(H5N1) hemagglutinin show that the Q226H mutation alters binding toward human-type α2-6-sialic acid receptors, indicating a molecular pathway for human adaptation.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
Supporting text

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.

Genes or proteins
hemagglutinin
Receptors
α2-6-sialylated glycan | human-type α2-6 sialic acid receptor
Mutations
Q226H
Mechanism types
receptor binding | receptor usage | host-range expansion
OVE11258 Molecular Adaptation
Key finding

A human case in British Columbia was infected with a clade 2.3.4.4b H5 virus of avian origin, indicating zoonotic spillover.

Virus
Influenza A virus H5N1
Host
birds Aves Natural host human Homo sapiens Natural host
Location
Canada
Supporting text

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. The global outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) among birds and the spillover to mammals increases the risk for humans.

Mechanism types
host tropism | host adaptation | adaptive mutation