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Originally published in Science Express on 5 February 2004
Science 19 March 2004:
Vol. 303. no. 5665, pp. 1838 - 1842
DOI: 10.1126/science.1093155
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Research Articles

The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin

S. J. Gamblin,1* L. F. Haire,1* R. J. Russell,1* D. J. Stevens,1 B. Xiao,1 Y. Ha,2{dagger} N. Vasisht,1 D. A. Steinhauer,1{ddagger} R. S. Daniels,1 A. Elliot,1 D. C. Wiley,2 J. J. Skehel1§

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibilitythat, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closelyrelated HAs in complex with receptor analogs. Theyexplain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.

1 Medical Research Council (MRC) National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
2 Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.


* These authors contributed equally to this work.

{dagger} Present address: Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

{ddagger} Present address: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.

§ To whom correspondence should be addressed. E-mail: mbrenna{at}nimr.mrc.ac.uk

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