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FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction

HIV-1 is dependent on the host cell for providing the metabolic resources for completion of its viral replication cycle. Thus, HIV-1 replicates efficiently only in activated CD4(+) T cells. Barriers preventing HIV-1 replication in resting CD4(+) T cells include a block that limits reverse transcript...

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Autores principales: Roux, Arthur, Leroy, Héloise, De Muylder, Bénédicte, Bracq, Lucie, Oussous, Samia, Dusanter-Fourt, Isabelle, Chougui, Ghina, Tacine, Rachida, Randriamampita, Clotilde, Desjardins, Delphine, Le Grand, Roger, Bouillaud, Frederic, Benichou, Serge, Margottin-Goguet, Florence, Cheynier, Remi, Bismuth, Georges, Mangeney, Marianne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513100/
https://www.ncbi.nlm.nih.gov/pubmed/31042779
http://dx.doi.org/10.1371/journal.ppat.1007669
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author Roux, Arthur
Leroy, Héloise
De Muylder, Bénédicte
Bracq, Lucie
Oussous, Samia
Dusanter-Fourt, Isabelle
Chougui, Ghina
Tacine, Rachida
Randriamampita, Clotilde
Desjardins, Delphine
Le Grand, Roger
Bouillaud, Frederic
Benichou, Serge
Margottin-Goguet, Florence
Cheynier, Remi
Bismuth, Georges
Mangeney, Marianne
author_facet Roux, Arthur
Leroy, Héloise
De Muylder, Bénédicte
Bracq, Lucie
Oussous, Samia
Dusanter-Fourt, Isabelle
Chougui, Ghina
Tacine, Rachida
Randriamampita, Clotilde
Desjardins, Delphine
Le Grand, Roger
Bouillaud, Frederic
Benichou, Serge
Margottin-Goguet, Florence
Cheynier, Remi
Bismuth, Georges
Mangeney, Marianne
author_sort Roux, Arthur
collection PubMed
description HIV-1 is dependent on the host cell for providing the metabolic resources for completion of its viral replication cycle. Thus, HIV-1 replicates efficiently only in activated CD4(+) T cells. Barriers preventing HIV-1 replication in resting CD4(+) T cells include a block that limits reverse transcription and also the lack of activity of several inducible transcription factors, such as NF-κB and NFAT. Because FOXO1 is a master regulator of T cell functions, we studied the effect of its inhibition on T cell/HIV-1 interactions. By using AS1842856, a FOXO1 pharmacologic inhibitor, we observe that FOXO1 inhibition induces a metabolic activation of T cells with a G0/G1 transition in the absence of any stimulatory signal. One parallel outcome of this change is the inhibition of the activity of the HIV restriction factor SAMHD1 and the activation of the NFAT pathway. FOXO1 inhibition by AS1842856 makes resting T cells permissive to HIV-1 infection. In addition, we found that FOXO1 inhibition by either AS1842856 treatment or upon FOXO1 knockdown induces the reactivation of HIV-1 latent proviruses in T cells. We conclude that FOXO1 has a central role in the HIV-1/T cell interaction and that inhibiting FOXO1 with drugs such as AS1842856 may be a new therapeutic shock-and-kill strategy to eliminate the HIV-1 reservoir in human T cells.
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spelling pubmed-65131002019-05-31 FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction Roux, Arthur Leroy, Héloise De Muylder, Bénédicte Bracq, Lucie Oussous, Samia Dusanter-Fourt, Isabelle Chougui, Ghina Tacine, Rachida Randriamampita, Clotilde Desjardins, Delphine Le Grand, Roger Bouillaud, Frederic Benichou, Serge Margottin-Goguet, Florence Cheynier, Remi Bismuth, Georges Mangeney, Marianne PLoS Pathog Research Article HIV-1 is dependent on the host cell for providing the metabolic resources for completion of its viral replication cycle. Thus, HIV-1 replicates efficiently only in activated CD4(+) T cells. Barriers preventing HIV-1 replication in resting CD4(+) T cells include a block that limits reverse transcription and also the lack of activity of several inducible transcription factors, such as NF-κB and NFAT. Because FOXO1 is a master regulator of T cell functions, we studied the effect of its inhibition on T cell/HIV-1 interactions. By using AS1842856, a FOXO1 pharmacologic inhibitor, we observe that FOXO1 inhibition induces a metabolic activation of T cells with a G0/G1 transition in the absence of any stimulatory signal. One parallel outcome of this change is the inhibition of the activity of the HIV restriction factor SAMHD1 and the activation of the NFAT pathway. FOXO1 inhibition by AS1842856 makes resting T cells permissive to HIV-1 infection. In addition, we found that FOXO1 inhibition by either AS1842856 treatment or upon FOXO1 knockdown induces the reactivation of HIV-1 latent proviruses in T cells. We conclude that FOXO1 has a central role in the HIV-1/T cell interaction and that inhibiting FOXO1 with drugs such as AS1842856 may be a new therapeutic shock-and-kill strategy to eliminate the HIV-1 reservoir in human T cells. Public Library of Science 2019-05-01 /pmc/articles/PMC6513100/ /pubmed/31042779 http://dx.doi.org/10.1371/journal.ppat.1007669 Text en © 2019 Roux et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Roux, Arthur
Leroy, Héloise
De Muylder, Bénédicte
Bracq, Lucie
Oussous, Samia
Dusanter-Fourt, Isabelle
Chougui, Ghina
Tacine, Rachida
Randriamampita, Clotilde
Desjardins, Delphine
Le Grand, Roger
Bouillaud, Frederic
Benichou, Serge
Margottin-Goguet, Florence
Cheynier, Remi
Bismuth, Georges
Mangeney, Marianne
FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction
title FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction
title_full FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction
title_fullStr FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction
title_full_unstemmed FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction
title_short FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction
title_sort foxo1 transcription factor plays a key role in t cell—hiv-1 interaction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513100/
https://www.ncbi.nlm.nih.gov/pubmed/31042779
http://dx.doi.org/10.1371/journal.ppat.1007669
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