A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth
Abstract Clade 2.3.4.4b H5N1 is causing an unprecedented outbreak in dairy cows in the United States. To understand if recent H5N1 viruses are changing their receptor use, we screened recombinant hemagglutinin (HA) from historical and recent 2.3.4.4b H5N1 viruses for binding to distinct glycans bear...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54934-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559322107052032 |
|---|---|
| author | Marina R. Good Monica L. Fernández-Quintero Wei Ji Alesandra J. Rodriguez Julianna Han Andrew B. Ward Jenna J. Guthmiller |
| author_facet | Marina R. Good Monica L. Fernández-Quintero Wei Ji Alesandra J. Rodriguez Julianna Han Andrew B. Ward Jenna J. Guthmiller |
| author_sort | Marina R. Good |
| collection | DOAJ |
| description | Abstract Clade 2.3.4.4b H5N1 is causing an unprecedented outbreak in dairy cows in the United States. To understand if recent H5N1 viruses are changing their receptor use, we screened recombinant hemagglutinin (HA) from historical and recent 2.3.4.4b H5N1 viruses for binding to distinct glycans bearing terminal sialic acids using a glycan microarray. We find that H5 from A/Texas/37/2024, an isolate from the dairy cow outbreak, has increased binding breadth to core glycans bearing terminal α2,3 sialic acids, the avian receptor, compared to historical and recent 2.3.4.4b H5N1 viruses. We do not observe any binding to α2,6 sialic acids, the receptor used by human seasonal influenza viruses. Using molecular dynamics and a cryo-EM structure of A/Texas/37/2024 H5, we show A/Texas/37/2024 H5 is more flexible within the receptor-binding site compared to a 2.3.4.4b H5 from 2022. We identify a single mutation outside of the receptor binding site, T199I, is responsible for increased binding breadth, as it increases receptor binding site flexibility. Together, these data show recent H5N1 viruses are evolving increased receptor binding breadth which could impact the host range and cell types infected with H5N1. |
| format | Article |
| id | doaj-art-dcf3c53f6415425ebc7ebed15b638817 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dcf3c53f6415425ebc7ebed15b6388172025-01-05T12:36:07ZengNature PortfolioNature Communications2041-17232024-12-0115111110.1038/s41467-024-54934-3A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadthMarina R. Good0Monica L. Fernández-Quintero1Wei Ji2Alesandra J. Rodriguez3Julianna Han4Andrew B. Ward5Jenna J. Guthmiller6Department of Immunology and Microbiology, University of Colorado Anschutz Medical CampusDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical CampusDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical CampusAbstract Clade 2.3.4.4b H5N1 is causing an unprecedented outbreak in dairy cows in the United States. To understand if recent H5N1 viruses are changing their receptor use, we screened recombinant hemagglutinin (HA) from historical and recent 2.3.4.4b H5N1 viruses for binding to distinct glycans bearing terminal sialic acids using a glycan microarray. We find that H5 from A/Texas/37/2024, an isolate from the dairy cow outbreak, has increased binding breadth to core glycans bearing terminal α2,3 sialic acids, the avian receptor, compared to historical and recent 2.3.4.4b H5N1 viruses. We do not observe any binding to α2,6 sialic acids, the receptor used by human seasonal influenza viruses. Using molecular dynamics and a cryo-EM structure of A/Texas/37/2024 H5, we show A/Texas/37/2024 H5 is more flexible within the receptor-binding site compared to a 2.3.4.4b H5 from 2022. We identify a single mutation outside of the receptor binding site, T199I, is responsible for increased binding breadth, as it increases receptor binding site flexibility. Together, these data show recent H5N1 viruses are evolving increased receptor binding breadth which could impact the host range and cell types infected with H5N1.https://doi.org/10.1038/s41467-024-54934-3 |
| spellingShingle | Marina R. Good Monica L. Fernández-Quintero Wei Ji Alesandra J. Rodriguez Julianna Han Andrew B. Ward Jenna J. Guthmiller A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth Nature Communications |
| title | A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth |
| title_full | A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth |
| title_fullStr | A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth |
| title_full_unstemmed | A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth |
| title_short | A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth |
| title_sort | single mutation in dairy cow associated h5n1 viruses increases receptor binding breadth |
| url | https://doi.org/10.1038/s41467-024-54934-3 |
| work_keys_str_mv | AT marinargood asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT monicalfernandezquintero asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT weiji asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT alesandrajrodriguez asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT juliannahan asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT andrewbward asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT jennajguthmiller asinglemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT marinargood singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT monicalfernandezquintero singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT weiji singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT alesandrajrodriguez singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT juliannahan singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT andrewbward singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth AT jennajguthmiller singlemutationindairycowassociatedh5n1virusesincreasesreceptorbindingbreadth |