title: IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle.
abstract: 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.
authors.affiliation: AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain. Electronic address: mcoiras@isciii.es.
authors.forename: Mayte
authors.initials: M
authors.lastname: Coiras
authors.affiliation: AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Bermejo
authors.affiliation: Institut de Génétique Humaine CNRS UPR1142, Université de Montpellier, Laboratoire de Virologie Moléculaire, Montpellier 34000, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Descours
authors.affiliation: AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Mateos
authors.affiliation: AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Pérez
authors.affiliation: AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain.
authors.forename: María-Rosa
authors.initials: MR
authors.lastname: López-Huertas
authors.affiliation: Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Institut de Génétique Humaine CNRS UPR1142, Université de Montpellier, Laboratoire de Virologie Moléculaire, Montpellier 34000, France.
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
authors.affiliation: AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain. Electronic address: ppalcami@isciii.es.
authors.forename: José
authors.initials: J
authors.lastname: Alcamí
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015851:Interleukin-7 / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D048348:Reverse Transcription; D000076106:SAM Domain and HD Domain-Containing Protein 1; D016662:Virus Integration
chemical_list: C508605:IL7 protein, human; D007376:Interleukin-2; D015851:Interleukin-7; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins