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.
Supporting text
Virus
Host
Location
Amino Acid Sequence
128
Amino Acid Substitution
81
Animals
1948
Antigenic Variation
14
Binding Sites
89
Birds
212
Carbohydrate Conformation
4
Cloning, Molecular
16
Crystallography, X-Ray
32
Glycosylation
22
Hemagglutinin Glycoproteins, Influenza Virus
180
Humans
1440
Influenza A Virus, H5N1 Subtype
300
Lung
65
Models, Molecular
99
Molecular Sequence Data
160
Mutation
209
Polysaccharides
31
Protein Conformation
44
Protein Folding
3
Protein Structure, Tertiary
29
Receptors, Virus
204
Respiratory Mucosa
10
Sialic Acids
29
