• Citer

Identification of Aryl Hydrocarbon Receptor as a Barrier to HIV-1 Infection and Outgrowth in CD4+ T-Cells (C. Van Lint and P. Ancuta are co-corresponding authors)

par Chatterjee, Debashree;Zhang, Yuwei;Ngassaki-Yoka, Christ-Dominique;Dutilleul, Antoine ;Khalil, Soumia;Hernalsteens, Olivier ;Wiche Salinas, Tomas Raul;Dias, Jonathan;Huicheng, Chen;Smail, Yasmine;Goulet, Jean-Philippe;Brendan, Bell;Routy, Jean-Pierre;Van Lint, Carine ;Ancuta, Petronela
Référence Cell reports, 42, 6, page (112634), doi:10.1016/j.celrep.2023.112634
Publication Publié, 2023-04-27

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

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.