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PMID: 16543414 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Science (New York, N.Y.) ·Vol. 312 ·No. 5772 ·2006-04-21 ·Pages 404-10

Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA

Abstract

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.

MeSH Terms
Amino Acid Sequence Amino Acid Substitution Animals Antigenic Variation Binding Sites Birds Carbohydrate Conformation Cloning, Molecular Crystallography, X-Ray Glycosylation Hemagglutinin Glycoproteins, Influenza Virus/chemistry,genetics,immunology,metabolism Humans Influenza A Virus, H5N1 Subtype/chemistry,genetics,metabolism,pathogenicity Lung/virology Models, Molecular Molecular Sequence Data Mutation Polysaccharides/metabolism Protein Conformation Protein Folding Protein Structure, Tertiary Receptors, Virus/chemistry,metabolism Respiratory Mucosa/virology Sialic Acids/chemistry,metabolism Species Specificity Virulence
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Polysaccharides Receptors, Virus Sialic Acids hemagglutinin, avian influenza A virus
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Stevens James
Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. [email protected]
Blixt Ola
Tumpey Terrence M
Taubenberger Jeffery K
Paulson James C
Wilson Ian A
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2006-04-21
Epub
2006-00-16
Pages
404-10
Language
English
Region
United States
NLM ID
0404511
Subset
IM
Grants
NIAID NIH HHS · AI058113 · United States
NIAID NIH HHS · AI42266 · United States
NCI NIH HHS · CA55896 · United States
NIGMS NIH HHS · GM060938 · United States
NIGMS NIH HHS · GM062116 · United States
Databases
PDB
Analysis Services
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