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Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike

Author

Listed:
  • Jeong Hyun Lee

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Daniel P. Leaman

    (The Scripps Research Institute)

  • Arthur S. Kim

    (The Scripps Research Institute)

  • Alba Torrents de la Peña

    (Academic Medical Center)

  • Kwinten Sliepen

    (Academic Medical Center)

  • Anila Yasmeen

    (Weill Medical College of Cornell University)

  • Ronald Derking

    (Academic Medical Center)

  • Alejandra Ramos

    (International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    The Scripps Research Institute)

  • Steven W. de Taeye

    (Academic Medical Center)

  • Gabriel Ozorowski

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Florian Klein

    (Laboratory of Molecular Immunology, The Rockefeller University)

  • Dennis R. Burton

    (International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    The Scripps Research Institute
    Ragon Institute of MGH, MIT and Harvard)

  • Michel C. Nussenzweig

    (Laboratory of Molecular Immunology, The Rockefeller University
    Howard Hughes Medical Institute, The Rockefeller University)

  • Pascal Poignard

    (International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    The Scripps Research Institute)

  • John P. Moore

    (Weill Medical College of Cornell University)

  • Per Johan Klasse

    (Weill Medical College of Cornell University)

  • Rogier W. Sanders

    (Academic Medical Center
    Weill Medical College of Cornell University)

  • Michael B. Zwick

    (The Scripps Research Institute)

  • Ian A. Wilson

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    Skaggs Institute for Chemical Biology, The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

Abstract

The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120–gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120–gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.

Suggested Citation

  • Jeong Hyun Lee & Daniel P. Leaman & Arthur S. Kim & Alba Torrents de la Peña & Kwinten Sliepen & Anila Yasmeen & Ronald Derking & Alejandra Ramos & Steven W. de Taeye & Gabriel Ozorowski & Florian Kle, 2015. "Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9167
    DOI: 10.1038/ncomms9167
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    Cited by:

    1. Jun Niu & Qi Wang & Wenwen Zhao & Bing Meng & Youwei Xu & Xianfang Zhang & Yi Feng & Qilian Qi & Yanling Hao & Xuan Zhang & Ying Liu & Jiangchao Xiang & Yiming Shao & Bei Yang, 2023. "Structures and immune recognition of Env trimers from two Asia prevalent HIV-1 CRFs," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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