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oai:repisalud.isciii.es:20.500.12105/89132025-05-16T11:14:32Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Coiras, Mayte author Bermejo, Mercedes author Descours, Benjamin author Mateos, Elena author García-Pérez, Javier author Lopez-Huertas, Maria Rosa author Lederman, Michael M author Benkirane, Monsef author Alcamí, José author 2016-03-08 HIV-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. Cell Rep. 2016 Mar 8;14(9):2100-2107. 10.1016/j.celrep.2016.02.022 2211-1247 22111247 Cell reports 26923586 http://hdl.handle.net/20.500.12105/8913 IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle