Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Autor: Stéphane Duquerroy, Christine Girard-Blanc, William Shepard, Wiyada Wongwiwat, Giovanna Barba-Spaeth, Stéphane Petres, Félix A. Rey, Pablo Guardado-Calvo, Ahmed Haouz, Juthathip Mongkolsapaya, M. Erika Navarro Sanchez, Carlos M. Kikuti, Wanwisa Dejnirattisai, Philippe Dussart, Fernando Arenzana-Seisdedos, Alexander Rouvinski, Marie-Christine Vaney, Philippe Desprès, Gavin R. Screaton
Přispěvatelé: Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11), Imperial College London, Protéopole, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur [Paris] (IP), Pathogénie Virale - Viral Pathogenesis, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Mahidol University [Bangkok], his work was made possible by a Pediatrics Dengue Vaccine Initiative grant to F.A.R., allowing the set up of a production facility of recombinant DENV sE. The co-crystallization with the bnAbs was done with European Union funding (DenFree consortium) to F.A.R. and G.R.S./J.M. F.A.R. acknowledges support from Insitut Pasteur, from the French Government’s ‘Investissements d’Avenir’ program: Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant number ANR-10-LABX-62-IBEID) and the CNRS. G.S.R. and J.M. were supported by the Medical Research Council, UK, the Wellcome Trust, UK, the National Institute for Health Research Biomedical Research Centre, Funding Scheme. G.R.S. is a Wellcome Trust Senior investigator. We thank staffs at beam lines PROXIMA-1 and PROXIMA-2 at the SOLEIL synchrotron (St Aubin, France) and ID23-2 and ID29 at the European Synchrotron Radiation Facility (Grenoble, France)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Tortosa, Pablo, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Pathogénie Virale, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical Research Council (MRC), Wellcome Trust, Commission of the European Communities, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Serotype
MECHANISM
Models
Molecular
MONOCLONAL-ANTIBODY
FAB FRAGMENTS
Protein Conformation
viruses
DROSOPHILA S2 CELLS
Dengue virus
medicine.disease_cause
Antibodies
Viral
Crystallography
X-Ray
Epitope
Dengue fever
Epitopes
FUSION
Viral Envelope Proteins
Virus maturation
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
0303 health sciences
Multidisciplinary
REFINEMENT
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
BORNE ENCEPHALITIS-VIRUS
ENVELOPE GLYCOPROTEIN
3. Good health
Multidisciplinary Sciences
Flavivirus
IMMATURE FLAVIVIRUS PARTICLES
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Science & Technology - Other Topics
[SDV.IMM]Life Sciences [q-bio]/Immunology
[SDV.IMM] Life Sciences [q-bio]/Immunology
General Science & Technology
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Molecular Sequence Data
Biology
Cross Reactions
Virus
MATURATION
03 medical and health sciences
Species Specificity
MD Multidisciplinary
medicine
Humans
Antibody-dependent enhancement
030304 developmental biology
Science & Technology
030306 microbiology
Dengue Virus
medicine.disease
biology.organism_classification
Virology
Antibodies
Neutralizing
Solubility
Mutation
Protein Multimerization
Zdroj: Nature
Nature, 2015, 520 (7545), pp.109-113. ⟨10.1038/nature14130⟩
Nature, Nature Publishing Group, 2015, 520 (7545), pp.109-113. ⟨10.1038/nature14130⟩
ISSN: 0028-0836
1476-4687
1476-4679
DOI: 10.1038/nature14130⟩
Popis: International audience; Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop and the two conserved glycan chains. This 'E-dimer-dependent epitope' is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell, explaining its conservation across serotypes and highlighting an Achilles' heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.
Databáze: OpenAIRE
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