The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism.

Autor:	Serris A; Institut Pasteur, Structural Virology Unit, and CNRS UMR 3569, Paris, France., Stass R; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK., Bignon EA; Fundación Ciencia & Vida, Molecular Virology Laboratory, Santiago, Chile; Universidad San Sebastián, Santiago, Chile., Muena NA; Fundación Ciencia & Vida, Molecular Virology Laboratory, Santiago, Chile., Manuguerra JC; Institut Pasteur, Unité Environnement et Risques Infectieux, Cellule d'Intervention Biologique d'Urgence (CIBU), Paris, France., Jangra RK; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA., Li S; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; School of Life Sciences, Tsinghua University, Beijing 100084, China., Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA., Tischler ND; Fundación Ciencia & Vida, Molecular Virology Laboratory, Santiago, Chile; Universidad San Sebastián, Santiago, Chile., Huiskonen JT; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; Helsinki Institute of Life Science HiLIFE, Viikinkaari 1, 00014 University of Helsinki, Finland; Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, Viikinkaari 1, 00014 University of Helsinki, Finland., Rey FA; Institut Pasteur, Structural Virology Unit, and CNRS UMR 3569, Paris, France. Electronic address: rey@pasteur.fr., Guardado-Calvo P; Institut Pasteur, Structural Virology Unit, and CNRS UMR 3569, Paris, France. Electronic address: guardado@pasteur.fr.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 Oct 15; Vol. 183 (2), pp. 442-456.e16. Date of Electronic Publication: 2020 Sep 15.
DOI:	10.1016/j.cell.2020.08.023
Abstrakt:	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-Å-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. Competing Interests: Declaration of Interests 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. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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