Receptor specificity of influenza A/H5 viruses including human 2003-04 isolates was studied. All but two isolates preserved high affinity to Sia2-3Gal (avian-like) receptors. However, two isolates (February, 2003, Hong Kong) demonstrated decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal (human-like) receptors. These two viruses had a unique Ser227-Asn change in the hemagglutinin molecule. Thus, a single amino acid substitution can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses. Asian 2003-04 H5 isolates from chickens and humans demonstrated highest affinity to the sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (Su-3'SLN) receptor but, in contrast to 1997 isolates, had increased affinity to fucosylated Su-3'SLN. American poultry H5 viruses also had increased affinity to Su-3'SLN. These data demonstrate that the genetic evolution of avian influenza A(H5N1) viruses is accompanied during adaptation to poultry by the evolution of their receptor specificity.
A Ser227-Asn substitution in the hemagglutinin of H5N1 influenza viruses changed receptor binding from avian-like Sia2-3Gal to human-like Sia2-6Gal, representing molecular adaptation toward human host receptors.
Two isolates (February, 2003, Hong Kong) demonstrated decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal receptors. These two viruses had a unique Ser227-Asn change in the hemagglutinin molecule. Thus, a single amino acid substitution can significantly alter receptor specificity of avian H5N1 viruses.
Genes or proteins
hemagglutinin
Receptors
Sia2-3Gal; Sia2-6Gal
Mutations
Ser227-Asn
Mechanism types
receptor_binding; host_range_adaptation
Molecular AdaptationExtraction confidence 0.90
Key finding
Asian and American poultry H5 influenza viruses evolved increased affinity to Su-3'SLN and fucosylated Su-3'SLN receptors, indicating receptor binding adaptation during poultry evolution of H5 viruses.
Asian 2003-04 H5 isolates from chickens and humans demonstrated highest affinity to the sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (Su-3'SLN) receptor but, in contrast to 1997 isolates, had increased affinity to fucosylated Su-3'SLN. American poultry H5 viruses also had increased affinity to Su-3'SLN.
Genes or proteins
hemagglutinin
Receptors
Su-3'SLN; fucosylated Su-3'SLN
Mechanism types
receptor_binding; adaptation_to_poultry
Receptor Usage2 records
Receptor UsageExtraction confidence 1.00
Key finding
Two Hong Kong 2003 H5N1 isolates with a Ser227-Asn substitution in hemagglutinin showed reduced binding to avian-type Sia2-3Gal and gained moderate affinity for human-type Sia2-6Gal receptors.
Receptor specificity of influenza A/H5 viruses including human 2003-04 isolates was studied. All but two isolates preserved high affinity to Sia2-3Gal (avian-like) receptors. However, two isolates (February, 2003, Hong Kong) demonstrated decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal (human-like) receptors. These two viruses had a unique Ser227-Asn change in the hemagglutinin molecule.
Method
receptor binding assay
Receptors
Sia2-3Gal; Sia2-6Gal
Receptor UsageExtraction confidence 1.00
Key finding
Asian 2003-04 avian and human H5N1 isolates showed strong binding to sulfated Su-3'SLN and increased affinity to fucosylated Su-3'SLN compared to 1997 strains, indicating evolution of receptor specificity during poultry adaptation.
Asian 2003-04 H5 isolates from chickens and humans demonstrated highest affinity to the sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (Su-3'SLN) receptor but, in contrast to 1997 isolates, had increased affinity to fucosylated Su-3'SLN. American poultry H5 viruses also had increased affinity to Su-3'SLN.
Method
receptor binding assay
Receptors
Su-3'SLN
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.90
Key finding
Sequence analysis identified a Ser227-Asn substitution in the hemagglutinin gene of H5N1 viruses that modified receptor specificity from avian-like to include human-like receptors.
Two isolates (February, 2003, Hong Kong) demonstrating decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal receptors had a unique Ser227-Asn change in the hemagglutinin molecule, showing that a single amino acid substitution can significantly alter receptor specificity of avian H5N1 viruses.
