Contribution of E190D and Q226H Mutations in HA to the Receptor-Binding Profile of D1.1 Genotype H5N1 Viruses.

Yang Fang1 Lei Yang1 Shumei Zou1 Liqi Liu1 Wenfei Zhu1 Dayan Wang1
Affiliations 1 institutions
  1. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (Chinese Academy of Preventive Medicine), Beijing, China.

Abstract

A 2024 human HPAI H5N1 case in British Columbia showed mixed viral populations containing HA-190D (28%) and HA-226H (35%) variants in tracheal aspirate sequencing. In this study, solid-phase binding assay and molecular docking were used to evaluate the contribution of HA-E190D/Q226H mutations to the viral receptor profiles. Our results showed that HA-E190D marginally reduced sialic acid α2,3 receptors' affinity, while HA-Q226H impaired both sialic acid α2,3 and α2,6 receptors' binding. These results demonstrate that neither mutation strengthens viral binding to human-type receptors, indicating that such substitutions are unlikely to heighten the public health threat posed by the virus for now.

Supporting text Virus Host Location
E190D 1 HPAI H5N1 6 public health threat 1 Q226H 1 receptor profile 1 Hemagglutinin Glycoproteins, Influenza Virus 180 Influenza A Virus, H5N1 Subtype 300 Mutation, Missense 26 Receptors, Virus 204 Virus Attachment 55 Amino Acid Substitution 81 Genotype 137 Humans 1440 Influenza, Human 286 Molecular Docking Simulation 5 Mutation 209 Protein Binding 193

Evidence records

3 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE11831
Key finding

Tracheal aspirate sequencing from a 2024 human HPAI H5N1 case in British Columbia detected mixed HA-190D (28%) and HA-226H (35%) variant populations.

Virus
Host
Location
Supporting text

A 2024 human HPAI H5N1 case in British Columbia showed mixed viral populations containing HA-190D (28%) and HA-226H (35%) variants in tracheal aspirate sequencing.

Method
sequencing
Sample type
tracheal aspirate
Geographic raw
British Columbia
Country inferred
CAN
Functional Mechanism
2 records · 1 evidence types
Evidence type
2 records
OVE11833
Key finding

In D1.1 genotype H5N1 viruses, the HA-Q226H substitution impairs binding to both sialic acid α2,3 and α2,6 receptors.

Virus
Host
Not specified
Location
Not specified
Supporting text

while HA-Q226H impaired both sialic acid α2,3 and α2,6 receptors' binding.

Method
solid-phase binding assay | molecular docking
Receptors
sialic acid α2,3 receptors | sialic acid α2,6 receptors
OVE11832
Key finding

In D1.1 genotype H5N1 viruses, the HA-E190D substitution marginally reduces affinity for sialic acid α2,3 receptors.

Virus
Host
Not specified
Location
Not specified
Supporting text

Our results showed that HA-E190D marginally reduced sialic acid α2,3 receptors' affinity

Method
solid-phase binding assay | molecular docking
Receptors
sialic acid α2,3 receptors