SRP191537 PRJNA531656 GSE129522 RNA-Seq of CD4+ T cells treated with AS1842856 or DMSO Quiescence is a hallmark of CD4+ T cells latently infected with HIV-1. While reversing this quiescence is an effective approach to reactivate latent HIV from T cells in culture, it can cause deleterious cytokine dysregulation in patients. Here we report that FOXO1, a key regulator of T-cell quiescence, promotes latency and suppresses productive HIV infection. In resting T cells, FOXO1 inhibition induces ER stress and activates two associated transcription factors: activating transcription factor 4 (ATF4) and nuclear factor of activated T cells (NFAT). Thus, our studies uncover a novel link between FOXO1, ER stress, and HIV infection that could be therapeutically exploited to selectively reverse T-cell quiescence and reduce the size of the latent viral reservoir. Overall design: RNA-Seq of CD4+ T cells from 3 donors treated with AS1842856 or DMSO for 12h and 48h GSE129522 pubmed 32541947