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Literature detail

Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus.

James Stevens1 Ola Blixt Terrence M Tumpey Jeffery K Taubenberger James C Paulson Ian A Wilson
Affiliations 1 institutions
  1. Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. [email protected]
PMID 16543414 2006 Science eng ppublish
PubMed DOI Browse context

Article

Publication summary

The hemagglutinin (HA) structure at 2.9 angstrom resolution, from a highly pathogenic Vietnamese H5N1 influenza virus, is more related to the 1918 and other human H1 HAs than to a 1997 duck H5 HA. Glycan microarray analysis of this Viet04 HA reveals an avian alpha2-3 sialic acid receptor binding preference. Introduction of mutations that can convert H1 serotype HAs to human alpha2-6 receptor specificity only enhanced or reduced affinity for avian-type receptors. However, mutations that can convert avian H2 and H3 HAs to human receptor specificity, when inserted onto the Viet04 H5 HA framework, permitted binding to a natural human alpha2-6 glycan, which suggests a path for this H5N1 virus to gain a foothold in the human population.

Amino Acid Sequence Amino Acid Substitution Animals Antigenic Variation Binding Sites Birds Carbohydrate Conformation Cloning, Molecular Crystallography, X-Ray Glycosylation Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Lung Models, Molecular Molecular Sequence Data Mutation Polysaccharides

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Mutations in the hemagglutinin of the Vietnamese H5N1 influenza virus enabled binding to human-type (alpha2-6) sialic acid receptors, indicating potential adaptation toward human hosts.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

Mutations that can convert avian H2 and H3 HAs to human receptor specificity, when inserted onto the Viet04 H5 HA framework, permitted binding to a natural human alpha2-6 glycan, which suggests a path for this H5N1 virus to gain a foothold in the human population.

Genes or proteins
hemagglutinin; HA
Receptors
alpha2-3 sialic acid receptor; alpha2-6 sialic acid receptor
Mechanism types
receptor_binding; host_range_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

The H5N1 Viet04 hemagglutinin binds preferentially to avian alpha2-3 sialic acid receptors, but specific mutations enable binding to human alpha2-6 sialic acid receptors.

Virus
IAV H5N1
Location
Not specified
Supporting text

Glycan microarray analysis of this Viet04 HA reveals an avian alpha2-3 sialic acid receptor binding preference. Mutations that can convert avian H2 and H3 HAs to human receptor specificity, when inserted onto the Viet04 H5 HA, permitted binding to a natural human alpha2-6 glycan.

Method
glycan microarray analysis; structural analysis
Receptors
sialic acid