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Molecular recognition of the native HIV-1 MPER revealed by STED microscopy of single virions

Author

Listed:
  • Pablo Carravilla

    (University of the Basque Country (UPV/EHU))

  • Jakub Chojnacki

    (University of Oxford)

  • Edurne Rujas

    (University of the Basque Country (UPV/EHU))

  • Sara Insausti

    (University of the Basque Country (UPV/EHU))

  • Eneko Largo

    (University of the Basque Country (UPV/EHU))

  • Dominic Waithe

    (University of Oxford)

  • Beatriz Apellaniz

    (University of the Basque Country (UPV/EHU))

  • Taylor Sicard

    (The Hospital for Sick Children Research Institute
    University of Toronto)

  • Jean-Philippe Julien

    (The Hospital for Sick Children Research Institute
    University of Toronto
    University of Toronto)

  • Christian Eggeling

    (University of Oxford
    Institute of Applied Optics Friedrich-Schiller-University Jena
    Leibniz Institute of Photonic Technology e.V.)

  • José L. Nieva

    (University of the Basque Country (UPV/EHU))

Abstract

Antibodies against the Membrane-Proximal External Region (MPER) of the Env gp41 subunit neutralize HIV-1 with exceptional breadth and potency. Due to the lack of knowledge on the MPER native structure and accessibility, different and exclusive models have been proposed for the molecular mechanism of MPER recognition by broadly neutralizing antibodies. Here, accessibility of antibodies to the native Env MPER on single virions has been addressed through STED microscopy. STED imaging of fluorescently labeled Fabs reveals a common pattern of native Env recognition for HIV-1 antibodies targeting MPER or the surface subunit gp120. In the case of anti-MPER antibodies, the process evolves with extra contribution of interactions with the viral lipid membrane to binding specificity. Our data provide biophysical insights into the recognition of the potent and broadly neutralizing MPER epitope on HIV virions, and as such is of importance for the design of therapeutic interventions.

Suggested Citation

  • Pablo Carravilla & Jakub Chojnacki & Edurne Rujas & Sara Insausti & Eneko Largo & Dominic Waithe & Beatriz Apellaniz & Taylor Sicard & Jean-Philippe Julien & Christian Eggeling & José L. Nieva, 2019. "Molecular recognition of the native HIV-1 MPER revealed by STED microscopy of single virions," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07962-9
    DOI: 10.1038/s41467-018-07962-9
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