Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation
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Sasisekharan_Networks link.pdf
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Author(s)
Soundararajan, Venkataramanan
Patel, Neel
Warnock, Ken
Wilson, Ian A.
Raguram, S.
Sasisekharan, V.
Sasisekharan, Ram
Zheng, Shu, M. Eng. Massachusetts Institute of Technology
Raman, Rahul
Date Issued
December 2011
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Soundararajan, Venkataramanan et al. “Networks Link Antigenic and Receptor-binding Sites of Influenza Hemagglutinin: Mechanistic Insight into Fitter Strain Propagation.” Scientific Reports 1 (2011): Web.
Version
Final published version
Abstract
Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are ‘linked’ to receptor-binding site (RBS) residues via their SIN and mutations within “RBS-linked” antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such “RBS-links” and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Singapore-MIT Alliance in Research and Technology (SMART)
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1038/srep00200
