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Structural HIV-1 Env Trimers Dynamics on Living T Cells

HIV research using multiphoton and fluorescence lifetime imaging

Diagram showing the structural conformations found from the FLIM phasor data. Diagram_of_HIV-1_particles_FLIM_phasor.jpg

The HIV-1 enveloped glycoprotein (Env), a trimeric spike-shaped surface protein, mediates viral fusion with the host cells. The interaction of HIV-1 Env with the host receptor CD4 is a crucial first step for virus-cell docking [Jakobsdottir et al. 2017]. This Env-CD4 interaction then triggers a number of conformational changes that allow the coreceptor (either CCR5 or CXCR4) to bind into the prebundle complex. These steps are required for viral fusion to take place and initiate cellular infection. Our group has previously shown the stoichiometry of these interactions in live cells utilizing time resolved two colour fluorescence fluctuation spectroscopy, combined with single virus tracking [Iliopoulou et al. 2018].

Read the full article:

Carlon-Andres, I., Malinauskas, T. & Padilla-Parra, S.:

Structure dynamics of HIV-1 Env trimers on native virions engaged with living T cells

Commun Biol 4, 1228 (2021).

In this article, we focus on the molecular mechanism of the Env protein as it interacts with T cell, the primary target of HIV-1 [Carlon-Andres I et al 2021]. Multiphoton and fluorescence lifetime imaging microscopy allow us to evaluate the inter and intramolecular dynamics of this process on the interface between the native virions and the live cells. We have found that Env cluster distribution is determined by the degree of maturation of virus particles and interrelates with the opening and closure of Env. Moreover, when exposing T cells with HIV-1 particles we found that different broadly neutralizing antibodies, targeting different epitopes, are able to disrupt Env cluster dynamics regardless Env epitope.

These results point to the importance of imaging HIV-1 particles when engaged with the host. In this setting, we show the importance of Env intermolecular association in immune evasion.

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