{"doi":"10.1016/j.celrep.2024.114414","title":"Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms","abstract":"The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms CD4 + T cells for increased HIV-1 replication/outgrowth. Consistently, colon-infiltrating CD4 + T cells carry replication-competent viral reservoirs in people with HIV-1 (PWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by monocytes, represents a rare event in ART-treated PWH, thus questioning the effect of RA on macrophages. Here, we demonstrate that RA enhances R5 but not X4 HIV-1 replication in monocyte-derived macrophages (MDMs). RNA sequencing, gene set variation analysis, and HIV interactor NCBI database interrogation reveal RA-mediated transcriptional reprogramming associated with metabolic/inflammatory processes and HIV-1 resistance/dependency factors. Functional validations uncover post-entry mechanisms of RA action including SAMHD1-modulated reverse transcription and CDK9/RNA polymerase II (RNAPII)-dependent transcription under the control of mammalian target of rapamycin (mTOR). These results support a model in which macrophages residing in the intestine of ART-untreated PWH contribute to viral replication/dissemination in an mTOR-sensitive manner.","journal":"Cell Reports","year":2024,"id":440655,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1029783,"name":"Amélie Cattin","orcid":"0000-0001-6741-5145","position":1,"is_corresponding":false},{"id":894398,"name":"Maryam Bendoumou","orcid":null,"position":2,"is_corresponding":false},{"id":1069193,"name":"Antoine Dutilleul","orcid":null,"position":3,"is_corresponding":false},{"id":1113462,"name":"Robert Lodge","orcid":"0000-0002-9908-0850","position":4,"is_corresponding":false},{"id":487405,"name":"Jean-Philippe Goulet","orcid":null,"position":5,"is_corresponding":false},{"id":1120496,"name":"Augustine Fert","orcid":null,"position":6,"is_corresponding":false},{"id":737994,"name":"Laurence Raymond Marchand","orcid":null,"position":7,"is_corresponding":false},{"id":343164,"name":"Tomas Raul Wiche Salinas","orcid":null,"position":8,"is_corresponding":false},{"id":1253090,"name":"Christ-Dominique Ngassaki Yoka","orcid":null,"position":9,"is_corresponding":false},{"id":737367,"name":"Etiene Moreira Gabriel","orcid":"0000-0002-3862-3030","position":10,"is_corresponding":false},{"id":1253091,"name":"Ramon Edwin Caballero","orcid":null,"position":11,"is_corresponding":false},{"id":673083,"name":"Jean-Pierre Routy","orcid":null,"position":12,"is_corresponding":false},{"id":1253092,"name":"Éric A. Cohen","orcid":null,"position":13,"is_corresponding":false},{"id":457360,"name":"Carine Van Lint","orcid":"0000-0002-2219-2862","position":14,"is_corresponding":false},{"id":18101,"name":"Petronela Ancuța","orcid":"0000-0003-1922-5640","position":15,"is_corresponding":false},{"id":1068701,"name":"Jonathan Dias","orcid":"0000-0002-7842-0115","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T02:01:01.842286Z","pmid":"38943643","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}