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Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein

The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic...

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Detalles Bibliográficos
Autores principales: Rissanen, Ilona, Stass, Robert, Krumm, Stefanie A, Seow, Jeffrey, Hulswit, Ruben JG, Paesen, Guido C, Hepojoki, Jussi, Vapalahti, Olli, Lundkvist, Åke, Reynard, Olivier, Volchkov, Viktor, Doores, Katie J, Huiskonen, Juha T, Bowden, Thomas A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755396/
https://www.ncbi.nlm.nih.gov/pubmed/33349334
http://dx.doi.org/10.7554/eLife.58242
Descripción
Sumario:The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryo-electron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc)(4) lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.