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Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus
James Stevens,1*Ola Blixt,1,2Terrence M. Tumpey,4Jeffery K. Taubenberger,5James C. Paulson,1,2Ian A. Wilson1,3*
The hemagglutinin (HA) structure at 2.9 angstrom resolution,from a highly pathogenic Vietnamese H5N1 influenza virus, ismore related to the 1918 and other human H1 HAs than to a 1997duck H5 HA. Glycan microarray analysis of this Viet04 HA revealsan avian 2-3 sialic acid receptor binding preference. Introductionof mutations that can convert H1 serotype HAs to human 2-6 receptorspecificity only enhanced or reduced affinity for avian-typereceptors. However, mutations that can convert avian H2 andH3 HAs to human receptor specificity, when inserted onto theViet04 H5 HA framework, permitted binding to a natural human2-6 glycan, which suggests a path for this H5N1 virus to gaina 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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