Coiras, MayteBermejo, MercedesDescours, BenjaminMateos, ElenaGarcía-Pérez, JavierLopez-Huertas, Maria RosaLederman, Michael MBenkirane, MonsefAlcamí, José2020-01-162020-01-162016-03-08Cell Rep. 2016 Mar 8;14(9):2100-2107.22111247http://hdl.handle.net/20.500.12105/8913HIV-1 post-integration latency in CD4+ lymphocytes is responsible for viral persistence despite treatment, but mechanisms involved in the establishment of latent viral reservoirs are not fully understood. We determined that both interleukin 2 (IL-2) and IL-7 induced SAMHD1 phosphorylation in T592, abrogating its antiviral activity. However, IL-7 caused a much more profound stimulatory effect on HIV-1 reverse transcription and integration than IL-2 that required chemokine co-stimulation. Both cytokines barely induced transcription due to low NF-κB induction, favoring the establishment of latent reservoirs. Effect of IL-7 on SAMHD1 phosphorylation was confirmed in IL-7-treated patients (ACTG 5214 study). Dasatinib--a tyrosine-kinase inhibitor--blocked SAMHD1 phosphorylation induced by IL-2 and IL-7 and restored HIV-1 restriction. We propose that γc-cytokines play a major role in the reservoir establishment not only by driving homeostatic proliferation but also by increasing susceptibility of CD4+ lymphocytes to HIV-1 infection through SAMHD1 inactivation.engVoRCD4-Positive T-LymphocytesCells, CulturedHIV-1HumansInterleukin-2Interleukin-7Monomeric GTP-Binding ProteinsPhosphorylationProtein Processing, Post-TranslationalReverse TranscriptionAttribution-NonCommercial-NoDerivatives 4.0 Internacional269235861492100-210710.1016/j.celrep.2016.02.0222211-1247Cell reportsopen access