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Your search keyword '"ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018)"' showing total 5 results
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5 results on '"ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018)"'

1. Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody

Author

Mittler, Eva, Serris, Alexandra, Esterman, Emma, Florez, Catalina, Polanco, Laura, O’brien, Cecilia, Slough, Megan, Tynell, Janne, Gröning, Remigius, Sun, Yan, Abelson, Dafna, Wec, Anna, Haslwanter, Denise, Keller, Markus, Ye, Chunyan, Bakken, Russel, Jangra, Rohit, Dye, John, Ahlm, Clas, Rappazzo, C. Garrett, Ulrich, Rainer, Zeitlin, Larry, Geoghegan, James, Bradfute, Steven, Sidoli, Simone, Forsell, Mattias N.E., Strandin, Tomas, Rey, Felix, Herbert, Andrew, Walker, Laura, Chandran, Kartik, Guardado-Calvo, Pablo, Albert Einstein College of Medicine [New York], Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Adimab [Lebanon], U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Umeå University, Mapp Biopharmaceutical Inc., Friedrich-Loeffler-Institut (FLI), The University of New Mexico [Albuquerque], Haaga-Helia University of Applied Sciences [Helsinki, Finland], This research was supported by NIAID of the NIH under award number U19AI142777 (Centers of Excellence in Translational Research) to K.C., L.M.W., J.M.D., A.S.H., S.B.B., M.N.E.F., and L.Z. M.N.E.F. was supported by a grant from the Swedish Research Council (no. 2020-06235). C.A. was supported by research grants from Region Västerbotten and Umeå University (RV-579011, RV-734361, and RV-965866). J.T. was supported by the Finnish Cultural Foundation (no. 00221066). R.K.J. was supported by grants from the NIH (R2AI156482, P20GM134974, and P20GM121307). R.G.U. was supported by the Bundesministerium für Bildung und Forschung (BMBF) within the Research Network Zoonotic Infectious Diseases (01KI1721A and 01KI2004A). T.S. was supported by the Academy of Finland (no. 321809). P.G.-C. was supported by a grant by the National French Research Agency (ANR-18-CE11-0011), and A.S. was supported with a fellowship by the French Fondation pour la Recherche Médicale (FDM20170638040). F.A.R. and P.G.-C. were supported by Labex IBEID (ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.

Published
2023
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2. Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses

Author

Eva Mittler, Anna Z. Wec, Janne Tynell, Pablo Guardado-Calvo, Julia Wigren-Byström, Laura C. Polanco, Cecilia M. O’Brien, Megan M. Slough, Dafna M. Abelson, Alexandra Serris, Mrunal Sakharkar, Gerard Pehau-Arnaudet, Russell R. Bakken, James C. Geoghegan, Rohit K. Jangra, Markus Keller, Larry Zeitlin, Olli Vapalahti, Rainer G. Ulrich, Zachary A. Bornholdt, Clas Ahlm, Felix A. Rey, John M. Dye, Steven B. Bradfute, Tomas Strandin, Andrew S. Herbert, Mattias N. E. Forsell, Laura M. Walker, Kartik Chandran, Albert Einstein College of Medicine [New York], Adimab [Lebanon], Umeå University, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Mapp Biopharmaceutical Inc., Institute of Novel and Emerging Infectious Diseases (INNT), Friedrich-Loeffler-Institut (FLI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, The University of New Mexico [Albuquerque], This research was supported by NIAID of the NIH under award number U19AI142777 (Centers of Excellence in Translational Research) to K.C., L.M.W., J.M.D., Z.A.B., A.S.H., S.B.B., M.N.E.F., and L.Z. M.N.E.F. was supported by a Consolidator grant from the Swedish Science Council (#2020-06235). C.A. was supported by a Cutting Edge Research Grant from Region Västerbotten (VLL-579011). T.S. was supported by the Academy of Finland (#321809). P.G.-C. was supported by a grant of the National French Research Agency (ANR-18-CE11-0011). A.S. was supported by a fellowship of the French Foundation pour la Recherche Médicale (FRM, fellowship FDM20170638040). F.A.R. and P.G.-C. were supported by Labex IBEID (ANR-10-LABX-62-IBEID). R.G.U. was supported by the Bundesministerium für Bildung und Forschung (BMBF) within the Research Network Zoonotic Infectious Diseases (01KI1721A and 01KI2004A)., ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
Orthohantavirus, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Hantavirus Infections, virus diseases, General Medicine, Antibodies, Viral, Antibodies, Neutralizing, Puumala virus, Article, Epitopes, Cricetinae, Hemorrhagic Fever with Renal Syndrome, Animals, Humans, Glycoproteins
Abstract

International audience; The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the “capping loop” of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.

Published
2022
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3. The Viral Class II Membrane Fusion Machinery: Divergent Evolution from an Ancestral Heterodimer

Author

Pablo Guardado-Calvo, Félix A. Rey, Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This research was funded by ANR, grant number ANR-18-CE11-0011, and Labex IBEID, grant number ANR-10-LABX-62-IBEID., ANR-18-CE11-0011,LISEFU,Base structurale de la détection des lipides dans la fusion virale(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)

Subjects
Conformational change, Bunyaviridae, Lipid Bilayers, Alphavirus, Review, bunyavirus, Genome, Viral, Microbiology, 03 medical and health sciences, Viral envelope, Virology, Animals, Humans, Lipid bilayer, class II fusion proteins, 030304 developmental biology, Glycoproteins, chemistry.chemical_classification, 0303 health sciences, structural homology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, 030306 microbiology, Chemistry, Membrane fusion protein, Virion, Lipid bilayer fusion, Virus Internalization, biology.organism_classification, Biological Evolution, QR1-502, Cell biology, Divergent evolution, Models, Structural, Infectious Diseases, Protein Multimerization, Glycoprotein, Viral Fusion Proteins
Abstract

International audience; A key step during the entry of enveloped viruses into cells is the merger of viral and cell lipid bilayers. This process is driven by a dedicated membrane fusion protein (MFP) present at the virion surface, which undergoes a membrane–fusogenic conformational change triggered by interactions with the target cell. Viral MFPs have been extensively studied structurally, and are divided into three classes depending on their three-dimensional fold. Because MFPs of the same class are found in otherwise unrelated viruses, their intra-class structural homology indicates horizontal gene exchange. We focus this review on the class II fusion machinery, which is composed of two glycoproteins that associate as heterodimers. They fold together in the ER of infected cells such that the MFP adopts a conformation primed to react to specific clues only upon contact with a target cell, avoiding premature fusion in the producer cell. We show that, despite having diverged in their 3D fold during evolution much more than the actual MFP, the class II accompanying proteins (AP) also derive from a distant common ancestor, displaying an invariant core formed by a β-ribbon and a C-terminal immunoglobulin-like domain playing different functional roles—heterotypic interactions with the MFP, and homotypic AP/AP contacts to form spikes, respectively. Our analysis shows that class II APs are easily identifiable with modern structural prediction algorithms, providing useful information in devising immunogens for vaccine design.

Published
2021
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4. The surface glycoproteins of hantaviruses

Author

Guardado-Calvo, Pablo, Rey, Félix, Virologie Structurale - Structural Virology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], We acknowledge support from the National French Research Agency (ANR-18-CE11-0011 to P.-G.C.), and Labex IBEID (ANR-10-LABX-62-IBEID to F.A.R. and P.-G.C.), 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), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
Orthohantavirus, Membrane Glycoproteins, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], viruses, Hantavirus Infections, Humans, RNA Viruses, Glycoproteins
Abstract

International audience; Hantaviruses are rodent-borne viruses distributed worldwide, transmitted through the air and with the ability to spread from person to person. They maintain a non-symptomatic persistent infection in their rodent hosts, but their spillover to humans produces a renal or pulmonary syndrome associated with high fatality rates. Hantavirus particles are lipid-enveloped and display a characteristic surface lattice built up of tetragonal spikes composed of two glycoproteins, Gn and Gc. The pleomorphism of these particles has hindered cryo-EM efforts to obtain detailed structural information and only by using a combination of X-ray crystallography and cryo-electron tomography it was possible to build an atomic model of the surface lattice. Here we review these structural efforts and the unanticipated evolutionary relations between hantaviruses and alphaviruses highlighted by these studies.

Published
2021
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5. The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism

Author

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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