A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity
Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new anti...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Nature Publishing Group
2024
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| Acceso en línea: | http://hdl.handle.net/20.500.12123/16493 https://www.nature.com/articles/s41467-023-42146-0 https://doi.org/10.1038/s41467-023-42146-0 |
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| author | Salmen, Wilhelm Hu, Liya Bok, Marina Chaimongkol, Natthawan Ettayebi, Khalil Sosnovtsev, Stanislav V. Soni, Kaundal Ayyar, B. Vijayalakshmi Shanker, Sreejesh Neill, Frederick H. Sankaran, Banumathi Atmar, Robert L. Estes, Mary K. Green, Kim Y. Parreño, Gladys Viviana Prasad, B. V. Venkataram |
| author_browse | Atmar, Robert L. Ayyar, B. Vijayalakshmi Bok, Marina Chaimongkol, Natthawan Estes, Mary K. Ettayebi, Khalil Green, Kim Y. Hu, Liya Neill, Frederick H. Parreño, Gladys Viviana Prasad, B. V. Venkataram Salmen, Wilhelm Sankaran, Banumathi Shanker, Sreejesh Soni, Kaundal Sosnovtsev, Stanislav V. |
| author_facet | Salmen, Wilhelm Hu, Liya Bok, Marina Chaimongkol, Natthawan Ettayebi, Khalil Sosnovtsev, Stanislav V. Soni, Kaundal Ayyar, B. Vijayalakshmi Shanker, Sreejesh Neill, Frederick H. Sankaran, Banumathi Atmar, Robert L. Estes, Mary K. Green, Kim Y. Parreño, Gladys Viviana Prasad, B. V. Venkataram |
| author_sort | Salmen, Wilhelm |
| collection | INTA Digital |
| description | Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection. |
| format | Artículo |
| id | INTA16493 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | Nature Publishing Group |
| publisherStr | Nature Publishing Group |
| record_format | dspace |
| spelling | INTA164932024-01-09T15:57:18Z A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity Salmen, Wilhelm Hu, Liya Bok, Marina Chaimongkol, Natthawan Ettayebi, Khalil Sosnovtsev, Stanislav V. Soni, Kaundal Ayyar, B. Vijayalakshmi Shanker, Sreejesh Neill, Frederick H. Sankaran, Banumathi Atmar, Robert L. Estes, Mary K. Green, Kim Y. Parreño, Gladys Viviana Prasad, B. V. Venkataram Antigens Nanotechnology Antígenos Nanotecnología Noroviruses Capsid Plasticity Norovirus Plasticidad de la Cápside Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection. Instituto de Virología Fil: Salmen, Wilhelm. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados Unidos Fil: Hu, Liya. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados Unidos Fil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnologicas; Argentina Fil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Chaimongkol, Natthawan. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados Unidos Fil: Ettayebi, Khalil. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unidos Fil: Sosnovtsev, Stanislav V. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados Unidos Fil: Soni, Kaundal. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados Unidos Fil: Ayyar, B. Vijayalakshmi. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unidos Fil: Shanker, Sreejesh. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados Unidos Fil: Neill, Frederick H. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unidos Fil: Sankaran, Banumathi. Berkeley Center for Structural Biology. Molecular Biophysics and Integrated Bioimaging. Lawrence Berkeley Laboratory; Estados Unidos Fil: Atmar, Robert L. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unidos Fil: Atmar, Robert L. Baylor College of Medicine. Department of Medicine; Estados Unidos Fil: Estes, Mary K. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unidos Fil: Estes, Mary K. Baylor College of Medicine. Department of Medicine; Estados Unidos Fil: Green, Kim Y. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados Unidos Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virologia e Innovaciones Tecnologicas (IVIT); Argentina Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Prasad, B. V. Venkataram. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados Unidos Fil: Prasad, B. V. Venkataram. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unidos 2024-01-09T15:51:32Z 2024-01-09T15:51:32Z 2023-10 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/16493 https://www.nature.com/articles/s41467-023-42146-0 2041-1723 https://doi.org/10.1038/s41467-023-42146-0 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Nature Publishing Group Nature Communications 14 : 6516 (Octubre 2023) |
| spellingShingle | Antigens Nanotechnology Antígenos Nanotecnología Noroviruses Capsid Plasticity Norovirus Plasticidad de la Cápside Salmen, Wilhelm Hu, Liya Bok, Marina Chaimongkol, Natthawan Ettayebi, Khalil Sosnovtsev, Stanislav V. Soni, Kaundal Ayyar, B. Vijayalakshmi Shanker, Sreejesh Neill, Frederick H. Sankaran, Banumathi Atmar, Robert L. Estes, Mary K. Green, Kim Y. Parreño, Gladys Viviana Prasad, B. V. Venkataram A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| title | A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| title_full | A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| title_fullStr | A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| title_full_unstemmed | A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| title_short | A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| title_sort | single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity |
| topic | Antigens Nanotechnology Antígenos Nanotecnología Noroviruses Capsid Plasticity Norovirus Plasticidad de la Cápside |
| url | http://hdl.handle.net/20.500.12123/16493 https://www.nature.com/articles/s41467-023-42146-0 https://doi.org/10.1038/s41467-023-42146-0 |
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