%0 Journal Article
%T Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms.
%A Dias J
%A Cattin A
%A Bendoumou M
%A Dutilleul A
%A Lodge R
%A Goulet JP
%A Fert A
%A Raymond Marchand L
%A Wiche Salinas TR
%A Ngassaki Yoka CD
%A Gabriel EM
%A Caballero RE
%A Routy JP
%A Cohen ÉA
%A Van Lint C
%A Ancuta P
%J Cell Rep
%V 43
%N 7
%D 2024 Jun 28
%M 38943643
暂无%R 10.1016/j.celrep.2024.114414
%X 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.