HIV infection leads to the induction of a program of quiescence

HIV persists in HIV+ individuals despite effective antiretroviral therapy due to the presence of a latent reservoir of transcriptionally silenced proviruses, primarily in quiescent CD4+ T cells. The transition of T cells into a quiescent state is closely associated with proviral latency and the seeding of this reservoir. However, the mechanisms governing the entry of HIV-infected T cells into quiescence remain poorly understood. Here, we show that HIV infection induces a quiescence program through the induction of KLF2 and the p53 pathway, leading to the downregulation of MYC and the suppression of proliferative and metabolic pathways. This results in the entry of cells into quiescence and, in a subset of cases, the establishment of proviral latency. These findings reveal a novel HIV-induced mechanism for the formation of the latent reservoir and offer new insights into how viruses manipulate host cellular programs.