1. The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism
- Author
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Rohit K. Jangra, Eduardo A Bignon, Jean Claude Manuguerra, Sai Li, Juha T. Huiskonen, Robert Stass, Félix A. Rey, Nicole D. Tischler, Pablo Guardado-Calvo, Kartik Chandran, Nicolas A. Muena, Alexandra Serris, Institute of Biotechnology, Molecular and Integrative Biosciences Research Programme, Helsinki Institute of Life Science HiLIFE, Laboratory of Structural Biology, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Fundación Ciencia & Vida, Universidad San Sebastian, Environnement et Risques infectieux - Environment and Infectious Risks (ERI), Institut Pasteur [Paris] (IP), Cellule d'Intervention Biologique d'Urgence (Centre National de Référence) - Laboratory for Urgent Response to Biological Threats (National Reference Center) (CIBU), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), Albert Einstein College of Medicine [New York], Tsinghua University [Beijing] (THU), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Faculty of Biological and Environmental Sciences [Helsinki], 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 Médicale (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 Investigación 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., ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-15-IFEC-0008,HantaHunt,Structure and function analyses of the Hantavirus envelope glycoproteins and their role in virus assembly, virus entry and immune recognition, as novel targets for antiviral treatment(2015), European Project: 649053,H2020,ERC-2014-CoG,BIZEB(2015), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut Pasteur [Paris], and University of Helsinki
- Subjects
CONFORMATIONAL-CHANGES ,Orthohantavirus ,Immunogen ,Protein Conformation ,viruses ,membrane fusion ,virus assembly ,PROTEIN ,class-II fusion protein ,virus entry ,0302 clinical medicine ,Viral Envelope Proteins ,CRYSTAL-STRUCTURE ,chemistry.chemical_classification ,0303 health sciences ,Membrane Glycoproteins ,hantaviruses ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,ENVELOPE GLYCOPROTEIN ,STRUCTURAL BASIS ,medicine.drug_class ,viral surface glycoprotein layer ,MEMBRANE-FUSION ,Biology ,Endocytosis ,Monoclonal antibody ,bunyaviruses ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Viral entry ,medicine ,RNA Viruses ,Hantaan virus ,Glycoproteins ,030304 developmental biology ,Hantavirus ,hantavirus pulmonary sydnrome ,HANTAAN-VIRUS ,TO-PERSON TRANSMISSION ,Virion ,Lipid bilayer fusion ,Virus Internalization ,ENCEPHALITIS-VIRUS ,Virology ,chemistry ,1182 Biochemistry, cell and molecular biology ,MONOCLONAL-ANTIBODIES ,virus structure ,Glycoprotein ,030217 neurology & neurosurgery - 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-angstrom-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.
- Published
- 2020
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