Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin
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Srinivasan-2013-Quantitative descrip.pdf
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Author(s)
Srinivasan, Karunya
Raman, Rahul
Jayaraman, Akila
Viswanathan, Karthik
Sasisekharan, Ram
Date Issued
February 2013
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Srinivasan, Karunya, Rahul Raman, Akila Jayaraman, Karthik Viswanathan, and Ram Sasisekharan 2013Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin. Earl G. Brown, ed. PLoS ONE 8(2): e49597.
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Final published version
Abstract
In the context of recently emerged novel influenza strains through reassortment, avian influenza subtypes such as H5N1, H7N7, H7N2, H7N3 and H9N2 pose a constant threat in terms of their adaptation to the human host. Among these subtypes, it was recently demonstrated that mutations in H5 and H9 hemagglutinin (HA) in the context of lab-generated reassorted viruses conferred aerosol transmissibility in ferrets (a property shared by human adapted viruses). We previously demonstrated that the quantitative binding affinity of HA to α2→6 sialylated glycans (human receptors) is one of the important factors governing human adaptation of HA. Although the H7 subtype has infected humans causing varied clinical outcomes from mild conjunctivitis to severe respiratory illnesses, it is not clear where the HA of these subtypes stand in regard to human adaptation since its binding affinity to glycan receptors has not yet been quantified. In this study, we have quantitatively characterized the glycan receptor-binding specificity of HAs from representative strains of Eurasian (H7N7) and North American (H7N2) lineages that have caused human infection. Furthermore, we have demonstrated for the first time that two specific mutations; Gln226→Leu and Gly228→Ser in glycan receptor-binding site of H7 HA substantially increase its binding affinity to human receptor. Our findings contribute to a framework for monitoring the evolution of H7 HA to be able to adapt to human host.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. School of Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0049597
