Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants
Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101658 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 |
| _version_ | 1826201012232257536 |
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| author | Zhu, Xueyong Viswanathan, Karthik Raman, Rahul Yu, Wenli Sasisekharan, Ram Wilson, Ian A. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Zhu, Xueyong Viswanathan, Karthik Raman, Rahul Yu, Wenli Sasisekharan, Ram Wilson, Ian A. |
| author_sort | Zhu, Xueyong |
| collection | MIT |
| description | Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Vietnam/1203/2004 and A/Indonesia/5/2005 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6-linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3-linked sialosides. Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogs reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses. |
| first_indexed | 2024-09-23T11:44:58Z |
| format | Article |
| id | mit-1721.1/101658 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:44:58Z |
| publishDate | 2016 |
| publisher | Elsevier |
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| spelling | mit-1721.1/1016582022-09-27T21:40:44Z Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants Zhu, Xueyong Viswanathan, Karthik Raman, Rahul Yu, Wenli Sasisekharan, Ram Wilson, Ian A. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. School of Engineering Koch Institute for Integrative Cancer Research at MIT Viswanathan, Karthik Raman, Rahul Sasisekharan, Ram Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Vietnam/1203/2004 and A/Indonesia/5/2005 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6-linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3-linked sialosides. Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogs reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses. Skaggs Institute for Chemical Biology National Institutes of Health (U.S.) (Merit Award R37 GM057073-13) National Institute of Allergy and Infectious Diseases (U.S.) (R01AI111395) Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology) Skolkovo Foundation 2016-03-10T03:11:13Z 2016-03-10T03:11:13Z 2015-11 2015-10 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/101658 Zhu, Xueyong, Karthik Viswanathan, Rahul Raman, Wenli Yu, Ram Sasisekharan, and Ian A. Wilson. “Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants.” Cell Reports 13, no. 8 (November 2015): 1683–1691. https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 en_US http://dx.doi.org/10.1016/j.celrep.2015.10.027 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Zhu, Xueyong Viswanathan, Karthik Raman, Rahul Yu, Wenli Sasisekharan, Ram Wilson, Ian A. Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants |
| title | Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants |
| title_full | Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants |
| title_fullStr | Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants |
| title_full_unstemmed | Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants |
| title_short | Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants |
| title_sort | structural basis for a switch in receptor binding specificity of two h5n1 hemagglutinin mutants |
| url | http://hdl.handle.net/1721.1/101658 https://orcid.org/0000-0002-1288-9965 https://orcid.org/0000-0002-2085-7840 |
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