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Renée Marije van der Sluis

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway. / van Montfort, Thijs; van der Sluis, Renée; Darcis, Gilles; Beaty, Doyle; Groen, Kevin; Pasternak, Alexander O; Pollakis, Georgios; Vink, Monique; Westerhout, Ellen M; Hamdi, Mohamed; Bakker, Margreet; van der Putten, Boas; Jurriaans, Suzanne; Prins, Jan H; Jeeninga, Rienk; Thomas, Adri A M; Speijer, Dave; Berkhout, Ben.

I: EBioMedicine, Bind 42, 26.04.2019, s. 97-108.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

van Montfort, T, van der Sluis, R, Darcis, G, Beaty, D, Groen, K, Pasternak, AO, Pollakis, G, Vink, M, Westerhout, EM, Hamdi, M, Bakker, M, van der Putten, B, Jurriaans, S, Prins, JH, Jeeninga, R, Thomas, AAM, Speijer, D & Berkhout, B 2019, 'Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway', EBioMedicine, bind 42, s. 97-108. https://doi.org/10.1016/j.ebiom.2019.02.014

APA

van Montfort, T., van der Sluis, R., Darcis, G., Beaty, D., Groen, K., Pasternak, A. O., Pollakis, G., Vink, M., Westerhout, E. M., Hamdi, M., Bakker, M., van der Putten, B., Jurriaans, S., Prins, J. H., Jeeninga, R., Thomas, A. A. M., Speijer, D., & Berkhout, B. (2019). Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway. EBioMedicine, 42, 97-108. https://doi.org/10.1016/j.ebiom.2019.02.014

CBE

van Montfort T, van der Sluis R, Darcis G, Beaty D, Groen K, Pasternak AO, Pollakis G, Vink M, Westerhout EM, Hamdi M, Bakker M, van der Putten B, Jurriaans S, Prins JH, Jeeninga R, Thomas AAM, Speijer D, Berkhout B. 2019. Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway. EBioMedicine. 42:97-108. https://doi.org/10.1016/j.ebiom.2019.02.014

MLA

Vancouver

Author

van Montfort, Thijs ; van der Sluis, Renée ; Darcis, Gilles ; Beaty, Doyle ; Groen, Kevin ; Pasternak, Alexander O ; Pollakis, Georgios ; Vink, Monique ; Westerhout, Ellen M ; Hamdi, Mohamed ; Bakker, Margreet ; van der Putten, Boas ; Jurriaans, Suzanne ; Prins, Jan H ; Jeeninga, Rienk ; Thomas, Adri A M ; Speijer, Dave ; Berkhout, Ben. / Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway. I: EBioMedicine. 2019 ; Bind 42. s. 97-108.

Bibtex

@article{acb59fcc9a2c446d8869efd78c5caf9d,
title = "Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway",
abstract = "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.",
keywords = "Activated T cells, Akt, Dendritic cells, Latency, PI3K, mTOR",
author = "{van Montfort}, Thijs and {van der Sluis}, Ren{\'e}e and Gilles Darcis and Doyle Beaty and Kevin Groen and Pasternak, {Alexander O} and Georgios Pollakis and Monique Vink and Westerhout, {Ellen M} and Mohamed Hamdi and Margreet Bakker and {van der Putten}, Boas and Suzanne Jurriaans and Prins, {Jan H} and Rienk Jeeninga and Thomas, {Adri A M} and Dave Speijer and Ben Berkhout",
note = "Copyright {\textcopyright} 2019. Published by Elsevier B.V.",
year = "2019",
month = apr,
day = "26",
doi = "10.1016/j.ebiom.2019.02.014",
language = "English",
volume = "42",
pages = "97--108",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Dendritic cells potently purge latent HIV-1 beyond TCR-stimulation, activating the PI3K-Akt-mTOR pathway

AU - van Montfort, Thijs

AU - van der Sluis, Renée

AU - Darcis, Gilles

AU - Beaty, Doyle

AU - Groen, Kevin

AU - Pasternak, Alexander O

AU - Pollakis, Georgios

AU - Vink, Monique

AU - Westerhout, Ellen M

AU - Hamdi, Mohamed

AU - Bakker, Margreet

AU - van der Putten, Boas

AU - Jurriaans, Suzanne

AU - Prins, Jan H

AU - Jeeninga, Rienk

AU - Thomas, Adri A M

AU - Speijer, Dave

AU - Berkhout, Ben

N1 - Copyright © 2019. Published by Elsevier B.V.

PY - 2019/4/26

Y1 - 2019/4/26

N2 - 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.

AB - 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.

KW - Activated T cells

KW - Akt

KW - Dendritic cells

KW - Latency

KW - PI3K

KW - mTOR

U2 - 10.1016/j.ebiom.2019.02.014

DO - 10.1016/j.ebiom.2019.02.014

M3 - Journal article

C2 - 30824386

VL - 42

SP - 97

EP - 108

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -