A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity

Autores
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
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Fuente
Nature Communications 14 : 6516 (Octubre 2023)
Materia
Antigens
Nanotechnology
Antígenos
Nanotecnología
Noroviruses
Capsid Plasticity
Norovirus
Plasticidad de la Cápside
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/16493
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oai_identifier_str oai:localhost:20.500.12123/16493
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spelling A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticitySalmen, WilhelmHu, LiyaBok, MarinaChaimongkol, NatthawanEttayebi, KhalilSosnovtsev, Stanislav V.Soni, KaundalAyyar, B. VijayalakshmiShanker, SreejeshNeill, Frederick H.Sankaran, BanumathiAtmar, Robert L.Estes, Mary K.Green, Kim Y.Parreño, Gladys VivianaPrasad, B. V. VenkataramAntigensNanotechnologyAntígenosNanotecnologíaNorovirusesCapsid PlasticityNorovirusPlasticidad de la CápsideAcute 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 VirologíaFil: Salmen, Wilhelm. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Hu, Liya. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnologicas; ArgentinaFil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chaimongkol, Natthawan. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Ettayebi, Khalil. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sosnovtsev, Stanislav V. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Soni, Kaundal. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Ayyar, B. Vijayalakshmi. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Shanker, Sreejesh. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Neill, Frederick H. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sankaran, Banumathi. Berkeley Center for Structural Biology. Molecular Biophysics and Integrated Bioimaging. Lawrence Berkeley Laboratory; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Green, Kim Y. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosNature Publishing Group2024-01-09T15:51:32Z2024-01-09T15:51:32Z2023-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/16493https://www.nature.com/articles/s41467-023-42146-02041-1723https://doi.org/10.1038/s41467-023-42146-0Nature Communications 14 : 6516 (Octubre 2023)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-11T10:24:55Zoai:localhost:20.500.12123/16493instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-11 10:24:56.097INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv 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
spellingShingle A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity
Salmen, Wilhelm
Antigens
Nanotechnology
Antígenos
Nanotecnología
Noroviruses
Capsid Plasticity
Norovirus
Plasticidad de la Cápside
title_short 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_sort A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity
dc.creator.none.fl_str_mv 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 Salmen, Wilhelm
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_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antigens
Nanotechnology
Antígenos
Nanotecnología
Noroviruses
Capsid Plasticity
Norovirus
Plasticidad de la Cápside
topic Antigens
Nanotechnology
Antígenos
Nanotecnología
Noroviruses
Capsid Plasticity
Norovirus
Plasticidad de la Cápside
dc.description.none.fl_txt_mv 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
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.
publishDate 2023
dc.date.none.fl_str_mv 2023-10
2024-01-09T15:51:32Z
2024-01-09T15:51:32Z
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 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
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
identifier_str_mv 2041-1723
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Nature Communications 14 : 6516 (Octubre 2023)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
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instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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