Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein.
Elife
; 92020 12 22.
Article
en En
| MEDLINE
| ID: mdl-33349334
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Proteínas Virales de Fusión
/
Virus Puumala
/
Anticuerpos Neutralizantes
/
Anticuerpos Antivirales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
Reino Unido