Autor: |
Ilona Rissanen, Robert Stass, Stefanie A Krumm, Jeffrey Seow, Ruben JG Hulswit, Guido C Paesen, Jussi Hepojoki, Olli Vapalahti, Åke Lundkvist, Olivier Reynard, Viktor Volchkov, Katie J Doores, Juha T Huiskonen, Thomas A Bowden |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
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Zdroj: |
eLife, Vol 9 (2020) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.58242 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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