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

• Published in: Nature communications Vol. 10; no. 1; p. 78
• Main Authors: Carravilla, Pablo, Chojnacki, Jakub, Rujas, Edurne, Insausti, Sara, Largo, Eneko, Waithe, Dominic, Apellaniz, Beatriz, Sicard, Taylor, Julien, Jean-Philippe, Eggeling, Christian, Nieva, José L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.01.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Accessibility; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - metabolism; Epitopes; Epitopes - chemistry; Epitopes - immunology; Fluorescent Dyes - chemistry; Glycoprotein gp120; Glycoprotein gp41; HEK293 Cells; HIV; HIV Antibodies - immunology; HIV Antibodies - metabolism; HIV Envelope Protein gp41 - immunology; HIV Envelope Protein gp41 - metabolism; HIV-1 - immunology; Human immunodeficiency virus; Humans; Image Processing, Computer-Assisted; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - immunology; Immunoglobulin Fab Fragments - metabolism; Immunoglobulins; Lipids; Microscopy; Microscopy, Fluorescence - methods; Molecular modelling; Neutralizing; Pattern recognition; Protein Binding - immunology; Therapeutic applications; Virion - immunology; Virion - metabolism; Virions
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07962-9

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.