Publication Date:
2006-03-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stevens, James -- Blixt, Ola -- Tumpey, Terrence M -- Taubenberger, Jeffery K -- Paulson, James C -- Wilson, Ian A -- AI058113/AI/NIAID NIH HHS/ -- AI42266/AI/NIAID NIH HHS/ -- CA55896/CA/NCI NIH HHS/ -- GM060938/GM/NIGMS NIH HHS/ -- GM062116/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2006 Apr 21;312(5772):404-10. Epub 2006 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. jstevens@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16543414" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
