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Originally published in Science Express on 16 March 2006
Science 21 April 2006:
Vol. 312. no. 5772, pp. 404 - 410
DOI: 10.1126/science.1124513
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Research Articles

Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus

James Stevens,1* Ola Blixt,1,2 Terrence M. Tumpey,4 Jeffery K. Taubenberger,5 James C. Paulson,1,2 Ian A. Wilson1,3*

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 {alpha}2-3 sialic acid receptor binding preference. Introduction of mutations that can convert H1 serotype HAs to human {alpha}2-6 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 {alpha}2-6 glycan, which suggests a path for this H5N1 virus to gain a foothold in the human population.

1 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Glycan Array Synthesis Core-D, Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
3 Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
4 Influenza Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
5 Department of Molecular Pathology, Armed Forces Institute of Pathology, Rockville, MD 20306, USA.

* To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu (I.A.W.) and jstevens{at}scripps.edu (J.S.)

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Thank You for the Influenza Articles
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Science Online, 12 May 2006 [Full text]

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