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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