Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway

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van Montfort, T, van der Sluis, R, Darcis, G, Beaty, D, Groen, K, Pasternak, AO, Pollakis, G ORCID: 0000-0002-9659-5461, Vink, M, Westerhout, EM, Hamdi, M et al (show 8 more authors) (2019) Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway. EBioMedicine, 42. pp. 97-108.

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Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway .pdf - Published version
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Official URL: http://dx.doi.org/10.1016/j.ebiom.2019.02.014

Abstract

© 2019 Background: The latent HIV-1 reservoir in treated patients primarily consists of resting memory CD4 + T cells. Stimulating the T-cell receptor (TCR), which facilitates transition of resting into effector T cells, is the most effective strategy to purge these latently infected cells. Here we supply evidence that TCR-stimulated effector T cells still frequently harbor latent HIV-1. Methods: Primary HIV-1 infected cells were used in a latency assay with or without dendritic cells (DCs) and reversion of HIV-1 latency was determined, in the presence or absence of specific pathway inhibitors. Findings: Renewed TCR-stimulation or subsequent activation with latency reversing agents (LRAs) did not overcome latency. However, interaction of infected effector cells with DCs triggered further activation of latent HIV-1. When compared to TCR-stimulation only, CD4 + T cells from aviremic patients receiving TCR + DC-stimulation reversed latency more frequently. Such a “one-two punch” strategy seems ideal for purging the reservoir. We determined that DC contact activates the PI3K-Akt-mTOR pathway in CD4 + T cells. Interpretation: This insight could facilitate the development of a novel class of potent LRAs that purge latent HIV beyond levels reached by T-cell activation.

Item Type:	Article
Uncontrolled Keywords:	Dendritic cells, Latency, PI3K, Akt, mTOR, Activated T cells
Depositing User:	Symplectic Admin
Date Deposited:	11 Mar 2019 11:45
Last Modified:	19 Jan 2023 00:57
DOI:	10.1016/j.ebiom.2019.02.014
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3034050