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 organization: Helsinki Institute of Life Science HiLIFE
Molecular and Integrative Biosciences Research Programme
Laboratory of Structural Biology
Helsinki One Health (HOH)
Viral Zoonosis Research Unit
Department of Virology
Medicum
Veterinary Biosciences
Olli Pekka Vapalahti / Principal Investigator
University Management
HUSLAB
Institute of Biotechnology
Date: 2020-12-22
Language: eng
Number of pages: 23
Belongs to series: eLife
ISSN: 2050-084X
DOI: https://doi.org/10.7554/eLife.58242
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.
Description: Rissanen, Ilona Stass, Robert Krumm, Stefanie A Seow, Jeffrey Hulswit, Ruben Jg Paesen, Guido C Hepojoki, Jussi Vapalahti, Olli Lundkvist, Ake Reynard, Olivier Volchkov, Viktor Doores, Katie J Huiskonen, Juha T Bowden, Thomas A eng MR/L009528/1/Medical Research Council/United Kingdom MR/S007555/1/Medical Research Council/United Kingdom MR/N002091/1/Medical Research Council/United Kingdom MR/K024426/1/Medical Research Council/United Kingdom 309605/Academy of Finland 649053/H2020 European Research Council 203141/Z/16Z/Wellcome Trust/United Kingdom 060208/Z/00/Z/Wellcome Trust/United Kingdom 093305/Z/10/Z/Wellcome Trust/United Kingdom England Elife. 2020 Dec 22;9. pii: 58242. doi: 10.7554/eLife.58242.
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
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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