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Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells

The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4(+) T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4(+) T cells in vi...

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Autores principales: Chatterjee, Debashree, Zhang, Yuwei, Ngassaki-Yoka, Christ-Dominique, Dutilleul, Antoine, Khalfi, Soumia, Hernalsteens, Olivier, Wiche Salinas, Tomas Raul, Dias, Jonathan, Chen, Huicheng, Smail, Yasmine, Goulet, Jean-Philippe, Bell, Brendan, Routy, Jean-Pierre, Lint, Carine Van, Ancuta, Petronela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592455/
https://www.ncbi.nlm.nih.gov/pubmed/37310858
http://dx.doi.org/10.1016/j.celrep.2023.112634
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author Chatterjee, Debashree
Zhang, Yuwei
Ngassaki-Yoka, Christ-Dominique
Dutilleul, Antoine
Khalfi, Soumia
Hernalsteens, Olivier
Wiche Salinas, Tomas Raul
Dias, Jonathan
Chen, Huicheng
Smail, Yasmine
Goulet, Jean-Philippe
Bell, Brendan
Routy, Jean-Pierre
Lint, Carine Van
Ancuta, Petronela
author_facet Chatterjee, Debashree
Zhang, Yuwei
Ngassaki-Yoka, Christ-Dominique
Dutilleul, Antoine
Khalfi, Soumia
Hernalsteens, Olivier
Wiche Salinas, Tomas Raul
Dias, Jonathan
Chen, Huicheng
Smail, Yasmine
Goulet, Jean-Philippe
Bell, Brendan
Routy, Jean-Pierre
Lint, Carine Van
Ancuta, Petronela
author_sort Chatterjee, Debashree
collection PubMed
description The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4(+) T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4(+) T cells in vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped HIV-1 infection, AhR blockade increases the efficacy of early/late reverse transcription and subsequently facilitated integration/translation. Moreover, AhR blockade boosts viral outgrowth in CD4(+) T cells of people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Finally, RNA sequencing reveals genes/pathways downregulated by AhR blockade in CD4(+) T cells of ART-treated PLWH, including HIV-1 interactors and gut-homing molecules with AhR-responsive elements in their promoters. Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency master regulator, is identified by chromatin immunoprecipitation as a direct AhR target. Thus, AhR governs a T cell transcriptional program controlling viral replication/outgrowth and tissue residency/recirculation, supporting the use of AhR inhibitors in “shock and kill” HIV-1 remission/cure strategies.
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spelling pubmed-105924552023-10-23 Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells Chatterjee, Debashree Zhang, Yuwei Ngassaki-Yoka, Christ-Dominique Dutilleul, Antoine Khalfi, Soumia Hernalsteens, Olivier Wiche Salinas, Tomas Raul Dias, Jonathan Chen, Huicheng Smail, Yasmine Goulet, Jean-Philippe Bell, Brendan Routy, Jean-Pierre Lint, Carine Van Ancuta, Petronela Cell Rep Article The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4(+) T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4(+) T cells in vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped HIV-1 infection, AhR blockade increases the efficacy of early/late reverse transcription and subsequently facilitated integration/translation. Moreover, AhR blockade boosts viral outgrowth in CD4(+) T cells of people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Finally, RNA sequencing reveals genes/pathways downregulated by AhR blockade in CD4(+) T cells of ART-treated PLWH, including HIV-1 interactors and gut-homing molecules with AhR-responsive elements in their promoters. Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency master regulator, is identified by chromatin immunoprecipitation as a direct AhR target. Thus, AhR governs a T cell transcriptional program controlling viral replication/outgrowth and tissue residency/recirculation, supporting the use of AhR inhibitors in “shock and kill” HIV-1 remission/cure strategies. 2023-06-27 2023-06-12 /pmc/articles/PMC10592455/ /pubmed/37310858 http://dx.doi.org/10.1016/j.celrep.2023.112634 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Chatterjee, Debashree
Zhang, Yuwei
Ngassaki-Yoka, Christ-Dominique
Dutilleul, Antoine
Khalfi, Soumia
Hernalsteens, Olivier
Wiche Salinas, Tomas Raul
Dias, Jonathan
Chen, Huicheng
Smail, Yasmine
Goulet, Jean-Philippe
Bell, Brendan
Routy, Jean-Pierre
Lint, Carine Van
Ancuta, Petronela
Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells
title Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells
title_full Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells
title_fullStr Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells
title_full_unstemmed Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells
title_short Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4(+) T cells
title_sort identification of aryl hydrocarbon receptor as a barrier to hiv-1 infection and outgrowth in cd4(+) t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592455/
https://www.ncbi.nlm.nih.gov/pubmed/37310858
http://dx.doi.org/10.1016/j.celrep.2023.112634
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