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

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Rissanen , I , Stass , R , Krumm , S A , Seow , J , Hulswit , R J G , Paesen , G C , Hepojoki , J , Vapalahti , O , Lundkvist , Å , Reynard , O , Volchkov , V , Doores , K J , Huiskonen , J T & Bowden , T A 2020 , ' Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein ' , eLife , vol. 9 , 58242 . https://doi.org/10.7554/eLife.58242

Title: Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
Author: Rissanen, Ilona; Stass, Robert; Krumm, Stefanie A.; Seow, Jeffrey; Hulswit, Ruben J.G.; Paesen, Guido C.; Hepojoki, Jussi; Vapalahti, O.; Lundkvist, Åke; Reynard, Olivier; Volchkov, Viktor; Doores, Katie J.; Huiskonen, Juha T.; Bowden, Thomas A.
Contributor: University of Helsinki, Helsinki Institute of Life Science HiLIFE
University of Helsinki, Helsinki One Health (HOH)
University of Helsinki, Department of Virology
University of Helsinki, Institute of Biotechnology
Date: 2020-12-22
Language: eng
Number of pages: 23
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/325000
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.
Subject: glycoprotein
hantavirus
infectious disease
microbiology
molecular biophysics
neutralizing antibody
structural biology
structure
viral fusion
virus declared
VIRUS ENVELOPE GLYCOPROTEINS
PUUMALA VIRUS
MONOCLONAL-ANTIBODIES
HEMORRHAGIC-FEVER
NEUTRALIZING ANTIBODIES
NEPHROPATHIA-EPIDEMICA
MEMBRANE-FUSION
SIN-NOMBRE
SYSTEM
PATHOGENESIS
11832 Microbiology and virology
3111 Biomedicine
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