Your browser doesn't support javascript.
loading
The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.
Sharma, Arvind; Zhang, Xiaokang; Dejnirattisai, Wanwisa; Dai, Xinghong; Gong, Danyang; Wongwiwat, Wiyada; Duquerroy, Stéphane; Rouvinski, Alexander; Vaney, Marie-Christine; Guardado-Calvo, Pablo; Haouz, Ahmed; England, Patrick; Sun, Ren; Zhou, Z Hong; Mongkolsapaya, Juthathip; Screaton, Gavin R; Rey, Felix A.
Afiliação
  • Sharma A; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France.
  • Zhang X; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France; Interdisciplinary Center for Brain Information, the Brain Cognition and Brain Disease Institute, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy o
  • Dejnirattisai W; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Dai X; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Gong D; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wongwiwat W; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Duquerroy S; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France; Université Paris-Saclay, Faculté des Sciences, F-91405 Orsay, France.
  • Rouvinski A; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France.
  • Vaney MC; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France.
  • Guardado-Calvo P; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France.
  • Haouz A; Institut Pasteur, Université de Paris, CNRS UMR 3528, Center for Technological Resources and Research, 75015 Paris, France.
  • England P; Institut Pasteur, Université de Paris, CNRS UMR 3528, Center for Technological Resources and Research, 75015 Paris, France.
  • Sun R; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zhou ZH; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Mongkolsapaya J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
  • Screaton GR; Division of Medical Sciences, University of Oxford, Oxford, UK. Electronic address: gavin.screaton@medsci.ox.ac.uk.
  • Rey FA; Institut Pasteur, Université de Paris, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France. Electronic address: felix.rey@pasteur.fr.
Cell ; 184(25): 6052-6066.e18, 2021 12 09.
Article em En | MEDLINE | ID: mdl-34852239
ABSTRACT
The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas do Envelope Viral / Dengue / Vírus da Dengue / Anticorpos Neutralizantes / Zika virus / Infecção por Zika virus Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: França
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas do Envelope Viral / Dengue / Vírus da Dengue / Anticorpos Neutralizantes / Zika virus / Infecção por Zika virus Limite: Animals / Humans Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: França