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.
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Nat Commun. 2019 Jan 8;10(1):78. 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.
针对 Env gp41 亚基膜近端外部区域（MPER）的抗体具有非凡的广度和效力，能够中和 HIV-1。由于对 MPER 天然结构和可及性缺乏了解，不同的和独特的模型已经被提出用于广泛中和抗体识别 MPER 的分子机制。在这里，通过 STED 显微镜解决了针对单病毒颗粒上天然 Env MPER 的抗体的可及性。荧光标记 Fab 的 STED 成像揭示了针对靶向 MPER 或表面亚基 gp120 的 HIV-1 抗体的天然 Env 识别的常见模式。在抗 MPER 抗体的情况下，该过程的进化需要与病毒脂质膜的额外相互作用来增加结合特异性。我们的数据为理解 HIV 病毒颗粒上有效且广泛中和的 MPER 表位的识别提供了生物物理见解，因此对于治疗干预的设计具有重要意义。
