Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus.
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.
Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. jstevens@scripps.edu
James
J
Stevens
Ola
O
Blixt
Terrence M
TM
Tumpey
Jeffery K
JK
Taubenberger
James C
JC
Paulson
Ian A
IA
Wilson
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000940:Antigenic Variation; D001665:Binding Sites; D001717:Birds; D002236:Carbohydrate Conformation; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D006031:Glycosylation; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D008168:Lung / Q000821:virology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011134:Polysaccharides / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000821:virology; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism; D013045:Species Specificity; D014774:Virulence
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011134:Polysaccharides; D011991:Receptors, Virus; D012794:Sialic Acids; C109963:hemagglutinin, avian influenza A virus