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Structure and Dynamics of HIV-1 Env Trimers on Native Virions Engaged in Living T Cells

39 Pages Posted: 19 May 2020 Sneak Peek Status: Under Review

See all articles by Irene Carlon-Andres

Irene Carlon-Andres

University of Oxford - Division of Structural Biology

Tomas Malinauskas

University of Oxford - Division of Structural Biology

Sergi Padilla-Parra

University of Oxford - Division of Structural Biology

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Abstract

The HIV-1 envelope glycoprotein (Env) mediates viral entry into the host cell. Although the highly dynamic nature of Env intramolecular conformations has been shown with single molecule spectroscopy in vitro, the bona fide Env intra and intermolecular mechanics when engaged in live T cells remains unknown. We used two photon fast fluorescence lifetime imaging detection of single-molecule Förster Resonance Energy Transfer occurring between fluorescent labels on HIV-1 Env. Our observations of Env dynamics reveal transitions between four intramolecular conformations of Env trimer and two additional intermolecular conformations that mediate Env clustering. Furthermore, we show that three broadly neutralizing anti-Env antibodies directed to different epitopes destabilise Env intermolecular dynamics and their clusters engaged to living T cells. Thus, this study illuminates how different conformations and clusters of Env mediate HIV-1 Env–T cell interactions in real time and therefore might control immune evasion.

Keywords: HIV-1 fusion, Env trimer dynamics, Env trimer clusters, HIV-1 broadly neutralizing antibodies, single molecule spectroscopy, two photon FRET-FLIM, Phasor Plot

Suggested Citation

Carlon-Andres, Irene and Malinauskas, Tomas and Padilla-Parra, Sergi, Structure and Dynamics of HIV-1 Env Trimers on Native Virions Engaged in Living T Cells. CELL-D-20-01229. Available at SSRN: https://ssrn.com/abstract=3589838 or http://dx.doi.org/10.2139/ssrn.3589838
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Irene Carlon-Andres

University of Oxford - Division of Structural Biology

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Tomas Malinauskas

University of Oxford - Division of Structural Biology

United Kingdom

Sergi Padilla-Parra (Contact Author)

University of Oxford - Division of Structural Biology

United Kingdom

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