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Nat Commun. 2019 Jan 8;10(1):78. doi: 10.1038/s41467-018-07962-9.

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

Author information

1
Biofisika Institute (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain.
2
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
3
Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, M5G 0A4, Canada.
4
Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
5
Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
6
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. christian.eggeling@rdm.ox.ac.uk.
7
Institute of Applied Optics Friedrich-Schiller-University Jena, Max-Wien Platz 4, 07743, Jena, Germany. christian.eggeling@rdm.ox.ac.uk.
8
Leibniz Institute of Photonic Technology e.V., Albert-Einstein-Straße 9, 07745, Jena, Germany. christian.eggeling@rdm.ox.ac.uk.
9
Biofisika Institute (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080, Bilbao, Spain. joseluis.nieva@ehu.es.

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.

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