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

• DOI: 10.1016/j.celrep.2023.112634
• Publication Date: 2023-06-12T10:50:05Z
• Authors: Debashree Chatterjee; Yuwei Zhang; Christ-Dominique ...; Antoine Dutilleul; Soumia Khalfi; Olivier Hernalsteens; Tomas Raul Wiche ...; Jonathan Dias; Huicheng Chen; Yasmine Smail; Jean-Philippe Goulet; Brendan Bell; Jean-Pierre Routy; Carine Van Lint; Petronela Ancuta
• Keywords: Chromatin immunoprecipitation

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 replication (TCR)-activated cells vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped infection, blockade increases the efficacy of early/late reverse transcription subsequently facilitated integration/translation. Moreover, boosts viral outgrowth people living with (PLWH) receiving antiretroviral therapy (ART). Finally, RNA sequencing reveals genes/pathways downregulated by ART-treated PLWH, including interactors gut-homing molecules AhR-responsive elements their promoters. Among them, HIC1, repressor Tat-mediated tissue-residency master regulator, is identified chromatin immunoprecipitation direct target. Thus, governs transcriptional program controlling tissue residency/recirculation, supporting use inhibitors "shock kill" remission/cure strategies.