Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity
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 framew...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/89056 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0002-6528-0125 |
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| author | Tharakaraman, Kannan Raman, Rahul Viswanathan, Karthik Stebbins, Nathan W. Jayaraman, Akila Krishnan, Arvind Sasisekharan, Ram Stebbins, Nathan W. Sasisekharan, Viswanathan |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Tharakaraman, Kannan Raman, Rahul Viswanathan, Karthik Stebbins, Nathan W. Jayaraman, Akila Krishnan, Arvind Sasisekharan, Ram Stebbins, Nathan W. Sasisekharan, Viswanathan |
| author_sort | Tharakaraman, Kannan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:17:04Z |
| format | Article |
| id | mit-1721.1/89056 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:17:04Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/890562022-10-02T01:55:54Z Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity Tharakaraman, Kannan Raman, Rahul Viswanathan, Karthik Stebbins, Nathan W. Jayaraman, Akila Krishnan, Arvind Sasisekharan, Ram Stebbins, Nathan W. Sasisekharan, Viswanathan Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Tharakaraman, Kannan Raman, Rahul Viswanathan, Karthik Stebbins, Nathan W. Jayaraman, Akila Krishnan, Arvind Sasisekharan, V. Sasisekharan, Ram 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. National Institutes of Health (U.S.) (R37 GM057073-13) Singapore-MIT Alliance for Research and Technology 2014-08-26T14:47:14Z 2014-08-26T14:47:14Z 2013-06 2013-05 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/89056 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. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0002-6528-0125 en_US http://dx.doi.org/10.1016/j.cell.2013.05.035 Cell 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. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Tharakaraman, Kannan Raman, Rahul Viswanathan, Karthik Stebbins, Nathan W. Jayaraman, Akila Krishnan, Arvind Sasisekharan, Ram Stebbins, Nathan W. Sasisekharan, Viswanathan Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity |
| title | Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity |
| title_full | Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity |
| title_fullStr | Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity |
| title_full_unstemmed | Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity |
| title_short | Structural Determinants for Naturally Evolving H5N1 Hemagglutinin to Switch Its Receptor Specificity |
| title_sort | structural determinants for naturally evolving h5n1 hemagglutinin to switch its receptor specificity |
| url | http://hdl.handle.net/1721.1/89056 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 https://orcid.org/0000-0002-6528-0125 |
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