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...

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Detalles Bibliográficos
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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Argentina
Institución:Instituto Nacional de Tecnología Agropecuaria
Repositorio:INTA Digital (INTA)
Idioma:inglés
OAI Identifier:oai:localhost:20.500.12123/16493
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
Access Level:acceso abierto
Palabra clave:Antigens
Nanotechnology
Antígenos
Nanotecnología
Noroviruses
Capsid Plasticity
Norovirus
Plasticidad de la Cápside
Descripción
Sumario: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.

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