Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity
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Sasisekharan_Structural determinants.pdf
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Author(s)
Tharakaraman, Kannan
Raman, Rahul
Viswanathan, Karthik
Stebbins, Nathan W.
Jayaraman, Akila
Krishnan, Arvind
Sasisekharan, Ram
Stebbins, Nathan W.
Sasisekharan, Viswanathan
Date Issued
June 2013
Journal
Cell
Publisher
Elsevier
Citation
Tharakaraman, Kannan, Rahul Raman, Karthik Viswanathan, Nathan W. Stebbins, Akila Jayaraman, Arvind Krishnan, V. Sasisekharan, and Ram Sasisekharan. “Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity.” Cell 153, no. 7 (June 2013): 1475–1485. © 2013 Elsevier Inc.
Version
Final published version
Abstract
Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to “quantitatively switch” its binding from avian to human glycan receptors. Here, we describe a structural framework that outlines a necessary set of H5 HA receptor-binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to a quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2013.05.035
