Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/76314 https://orcid.org/0000-0002-2085-7840 |
| _version_ | 1826195398887211008 |
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| author | 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 |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology 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 |
| author_sort | Soundararajan, Venkataramanan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:12:02Z |
| format | Article |
| id | mit-1721.1/76314 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:12:02Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/763142022-09-26T16:24:02Z Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation 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 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 Soundararajan, Venkataramanan Raman, Rahul Raguram, S. Sasisekharan, Ram Sasisekharan, V. Patel, Neel Shu, Zheng Warnock, Ken 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. National Institutes of Health (U.S.) (grant GM R37 GM057073-13) Singapore–MIT Alliance for Research and Technology National Institutes of Health (U.S.) (grant AI058113) 2013-01-18T19:33:25Z 2013-01-18T19:33:25Z 2011-12 2011-07 Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/76314 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. https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1038/srep00200 Scientific Reports Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | 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 Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation |
| title | Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation |
| title_full | Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation |
| title_fullStr | Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation |
| title_full_unstemmed | Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation |
| title_short | Networks link antigenic and receptor-binding sites of influenza hemagglutinin: Mechanistic insight into fitter strain propagation |
| title_sort | networks link antigenic and receptor binding sites of influenza hemagglutinin mechanistic insight into fitter strain propagation |
| url | http://hdl.handle.net/1721.1/76314 https://orcid.org/0000-0002-2085-7840 |
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