@article{2a82493cf23c4ea1b3913651705e0603,
title = "The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism",
abstract = "Hantaviruses are rodent-borne viruses causing serious zoonotic outbreaks worldwide for which no treatment is available. Hantavirus particles are pleomorphic and display a characteristic square surface lattice. The envelope glycoproteins Gn and Gc form heterodimers that further assemble into tetrameric spikes, the lattice building blocks. The glycoproteins, which are the sole targets of neutralizing antibodies, drive virus entry via receptor-mediated endocytosis and endosomal membrane fusion. Here we describe the high-resolution X-ray structures of the heterodimer of Gc and the Gn head and of the homotetrameric Gn base. Docking them into an 11.4-{\AA}-resolution cryoelectron tomography map of the hantavirus surface accounted for the complete extramembrane portion of the viral glycoprotein shell and allowed a detailed description of the surface organization of these pleomorphic virions. Our results, which further revealed a built-in mechanism controlling Gc membrane insertion for fusion, pave the way for immunogen design to protect against pathogenic hantaviruses.",
keywords = "bunyaviruses, class-II fusion protein, hantavirus pulmonary sydnrome, hantaviruses, membrane fusion, viral surface glycoprotein layer, virus assembly, virus entry, virus structure",
author = "Alexandra Serris and Robert Stass and Bignon, {Eduardo A.} and Muena, {Nicol{\'a}s A.} and Manuguerra, {Jean Claude} and Jangra, {Rohit K.} and Sai Li and Kartik Chandran and Tischler, {Nicole D.} and Huiskonen, {Juha T.} and Rey, {Felix A.} and Pablo Guardado-Calvo",
note = "Funding Information: We thank Ahmed Haouz and the staff of the Institut Pasteur protein crystallogenesis facility for help with crystallization trials; Fabrice Agou and the staff of the Chemogenomic and Biological Screening Platform for access to the MALS equipment; the staff of the PX1 and PX2 beamlines at synchrotron SOLEIL (St Aubin, France) for beamline support; and the Oxford Particle Imaging Centre, which was funded by a Wellcome Trust JIF award (060208/Z/00/Z) and is supported by an equipment grant from WT (093305/Z/10/Z). We thank Andreas Herrmann, Fran{\c c}ois Bontems, Gleyder Roman Sosa, Niels Volkmann, and Dorit Hanein for discussions. We acknowledge support from the National French Research Agency (ANR; ANR-18-CE11-0011 to F.A.R and P.-G.C.), the French Fondation pour la Recherche M{\'e}dicale (FRM; fellowship FDM20170638040 to A.S.), Labex IBEID (ANR-10-LABX-62-IBEID to F.A.R. and P.-G.C.), the Infect-ERA ANR-funded project “HantaHunt” (to F.A.R. and P.-G.C.), the European Research Council under the European Union Horizon 2020 Research and Innovation Program (649053 to J.T.H.), the National Institutes of Health (NIH; R01AI132633 to K.C.), Institut Pasteur and CNRS (to F.A.R. and P.-G.C.), the Chilean Agencia Nacional de Investigaci{\'o}n y Desarrollo (ANID, Chile; FONDECYT 1181799 to N.D.T.), and the ANID Programa de Apoyo a Centros con Financiamiento Basal 170004 (to N.D.T.). S.L. thanks Tsinghua University for providing startup funds. N.D.T. J.T.H. F.A.R. and P.G.-C. designed the experiments. A.S. expressed, purified, and crystallized the proteins. A.S. and P.G.-C. processed the crystallographic data. E.A.B. N.A.M. and N.D.T. prepared and analyzed the VLPs. R.S. S.L. and J.T.H. prepared samples for cryo-ET and collected and processed the data. J.-C.M. R.K.J. K.C. N.D.T. and J.T.H. analyzed the data. P.G.-C. and F.A.R. prepared the manuscript with input from all authors. E.A.B. N.D.T. F.A.R. and P.G.-C. are coinventors of a pending patent application for development of stabilized immunogens for an Andes virus vaccine. K.C. is a member of the scientific advisory board of Integrum Scientific, LLC. F.A.R. is on the board of Virtexx, SAS. Funding Information: We thank Ahmed Haouz and the staff of the Institut Pasteur protein crystallogenesis facility for help with crystallization trials; Fabrice Agou and the staff of the Chemogenomic and Biological Screening Platform for access to the MALS equipment; the staff of the PX1 and PX2 beamlines at synchrotron SOLEIL (St Aubin, France) for beamline support; and the Oxford Particle Imaging Centre, which was funded by a Wellcome Trust JIF award ( 060208/Z/00/Z ) and is supported by an equipment grant from WT ( 093305/Z/10/Z ). We thank Andreas Herrmann, Fran{\c c}ois Bontems, Gleyder Roman Sosa, Niels Volkmann, and Dorit Hanein for discussions. We acknowledge support from the National French Research Agency (ANR; ANR-18-CE11-0011 to F.A.R and P.-G.C.), the French Fondation pour la Recherche M{\'e}dicale (FRM; fellowship FDM20170638040 to A.S.), Labex IBEID ( ANR-10-LABX-62-IBEID to F.A.R. and P.-G.C.), the Infect-ERA ANR -funded project “HantaHunt” (to F.A.R. and P.-G.C.), the European Research Council under the European Union Horizon 2020 Research and Innovation Program ( 649053 to J.T.H.), the National Institutes of Health (NIH; R01AI132633 to K.C.), Institut Pasteur and CNRS (to F.A.R. and P.-G.C.), the Chilean Agencia Nacional de Investigaci{\'o}n y Desarrollo (ANID, Chile; FONDECYT 1181799 to N.D.T.), and the ANID Programa de Apoyo a Centros con Financiamiento Basal 170004 (to N.D.T.). S.L. thanks Tsinghua University for providing startup funds. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "15",
doi = "10.1016/j.cell.2020.08.023",
language = "English (US)",
volume = "183",
pages = "442--456.e16",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}