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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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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. |
format | Online Article Text |
id | pubmed-10592455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
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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