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Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages

Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a majo...

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Autores principales: Pasquereau, Sébastien, Kumar, Amit, Abbas, Wasim, Herbein, Georges
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923484/
https://www.ncbi.nlm.nih.gov/pubmed/29652795
http://dx.doi.org/10.3390/v10040190
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author Pasquereau, Sébastien
Kumar, Amit
Abbas, Wasim
Herbein, Georges
author_facet Pasquereau, Sébastien
Kumar, Amit
Abbas, Wasim
Herbein, Georges
author_sort Pasquereau, Sébastien
collection PubMed
description Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the in vitro effects of an HIV protease inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1 monocytoid cells. Ex vivo, we investigated the impact of combination antiretroviral therapy (cART) on Akt activation, as measured by flow cytometry, and on the viral reservoir size, quantified by qPCR, in monocytes and autologous resting CD4+ T cells from HIV-infected individuals (Trial registration: NCT02858414). We found that, in myeloid cells, both Akt activation and HIV-1 reactivation were inhibited by PI but not by NNRTI in vitro. Our results indicate that cART decreases Akt activation and reduces the size of the HIV reservoir in both monocytes and resting CD4+ T cells. Our study indicates that Akt activation could play a role in HIV reservoir formation, indicating that drugs which target Akt could be efficient for limiting its size in aviremic chronically infected patients.
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spelling pubmed-59234842018-05-03 Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages Pasquereau, Sébastien Kumar, Amit Abbas, Wasim Herbein, Georges Viruses Article Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the in vitro effects of an HIV protease inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1 monocytoid cells. Ex vivo, we investigated the impact of combination antiretroviral therapy (cART) on Akt activation, as measured by flow cytometry, and on the viral reservoir size, quantified by qPCR, in monocytes and autologous resting CD4+ T cells from HIV-infected individuals (Trial registration: NCT02858414). We found that, in myeloid cells, both Akt activation and HIV-1 reactivation were inhibited by PI but not by NNRTI in vitro. Our results indicate that cART decreases Akt activation and reduces the size of the HIV reservoir in both monocytes and resting CD4+ T cells. Our study indicates that Akt activation could play a role in HIV reservoir formation, indicating that drugs which target Akt could be efficient for limiting its size in aviremic chronically infected patients. MDPI 2018-04-13 /pmc/articles/PMC5923484/ /pubmed/29652795 http://dx.doi.org/10.3390/v10040190 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pasquereau, Sébastien
Kumar, Amit
Abbas, Wasim
Herbein, Georges
Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
title Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
title_full Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
title_fullStr Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
title_full_unstemmed Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
title_short Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
title_sort counteracting akt activation by hiv protease inhibitors in monocytes/macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923484/
https://www.ncbi.nlm.nih.gov/pubmed/29652795
http://dx.doi.org/10.3390/v10040190
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