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Published Online February 5, 2004
Science DOI: 10.1126/science.1093373

Reports

Submitted on November 6, 2003
Accepted on January 7, 2004

Structure of the Uncleaved Human H1 Hemagglutinin from the Extinct 1918 Influenza Virus

James Stevens 1, Adam L. Corper 1, Christopher F. Basler 2, Jeffery K. Taubenberger 3, Peter Palese 2, Ian A. Wilson 4*

1 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
3 Division of Molecular Pathology, Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
4 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

* To whom correspondence should be addressed. E-mail: wilson{at}scripps.edu.

The 1918 'Spanish' influenza pandemic represents the largest recorded outbreak of any infectious disease. The crystal structure of the uncleaved precursor of the major surface antigen of the extinct 1918 virus was determined at 3.0Å resolution after re-assembly of the hemagglutinin gene from viral RNA-fragments preserved in 1918 formalin-fixed lung tissues. A narrow, avian-like receptor binding site, two novel histidine patches and a less exposed surface loop at the cleavage site that activates viral membrane fusion reveals structural features primarily found in avian viruses, that may have contributed to the extraordinarily high infectivity and mortality rates observed during 1918.


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