Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin
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 hema...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2013
|
| Online Access: | http://hdl.handle.net/1721.1/78634 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 |
| _version_ | 1826212303408726016 |
|---|---|
| author | Srinivasan, Karunya Raman, Rahul Jayaraman, Akila Viswanathan, Karthik Sasisekharan, Ram |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Srinivasan, Karunya Raman, Rahul Jayaraman, Akila Viswanathan, Karthik Sasisekharan, Ram |
| author_sort | Srinivasan, Karunya |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:19:34Z |
| format | Article |
| id | mit-1721.1/78634 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:19:34Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/786342022-09-29T14:13:08Z Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin Srinivasan, Karunya Raman, Rahul Jayaraman, Akila Viswanathan, Karthik Sasisekharan, Ram 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 Srinivasan, Karunya Raman, Rahul Jayaraman, Akila Viswanathan, Karthik Sasisekharan, Ram 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. National Institutes of Health (U.S.) (GM R37 GM057073-13) Singapore-MIT Alliance for Research and Technology 2013-04-29T19:54:15Z 2013-04-29T19:54:15Z 2013-02 2012-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/78634 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. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1371/journal.pone.0049597 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Srinivasan, Karunya Raman, Rahul Jayaraman, Akila Viswanathan, Karthik Sasisekharan, Ram Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin |
| title | Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin |
| title_full | Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin |
| title_fullStr | Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin |
| title_full_unstemmed | Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin |
| title_short | Quantitative Description of Glycan-Receptor Binding of Influenza A Virus H7 Hemagglutinin |
| title_sort | quantitative description of glycan receptor binding of influenza a virus h7 hemagglutinin |
| url | http://hdl.handle.net/1721.1/78634 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 |
| work_keys_str_mv | AT srinivasankarunya quantitativedescriptionofglycanreceptorbindingofinfluenzaavirush7hemagglutinin AT ramanrahul quantitativedescriptionofglycanreceptorbindingofinfluenzaavirush7hemagglutinin AT jayaramanakila quantitativedescriptionofglycanreceptorbindingofinfluenzaavirush7hemagglutinin AT viswanathankarthik quantitativedescriptionofglycanreceptorbindingofinfluenzaavirush7hemagglutinin AT sasisekharanram quantitativedescriptionofglycanreceptorbindingofinfluenzaavirush7hemagglutinin |