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- Rissanen, Ilona, et al.
(author)
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Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
- 2020
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In: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 9
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Journal article (peer-reviewed)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, cryoelectron 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.
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