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dc.contributor.authorCoiras, Mayte 
dc.contributor.authorBermejo, Mercedes 
dc.contributor.authorDescours, Benjamin
dc.contributor.authorMateos, Elena 
dc.contributor.authorGarcía-Pérez, Javier 
dc.contributor.authorLopez-Huertas, Maria Rosa 
dc.contributor.authorLederman, Michael M
dc.contributor.authorBenkirane, Monsef
dc.contributor.authorAlcamí, José 
dc.date.accessioned2020-01-16T07:58:44Z
dc.date.available2020-01-16T07:58:44Z
dc.date.issued2016-03-08
dc.identifier.citationCell Rep. 2016 Mar 8;14(9):2100-2107.es_ES
dc.identifier.issn22111247es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8913
dc.description.abstractHIV-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.es_ES
dc.description.sponsorshipThe authors thank the patients for their participation in the study. We are indebted to Dr. Irini Sereti (NIAID, NIH), Amanda Zadzilka (Frontier Science and Technology Research Foundation), and Eugenia Aga (Harvard School of Public Health) for assistance with A5214 data and samples. We greatly appreciate the secretarial assistance of Mrs. Olga Palao. We thank the Centro Regional de Transfusión for supplying the buffy coats. We also thank Drs. Javier Martínez-Picado and Maria del Carmen Puertas (IrsiCaixa Institute) for their help with the standardization of qPCR in our laboratory. From Bristol-Myers Squibb, we especially acknowledge Drs. Stephen Mason and Carey Hwang for helpful discussion about this manuscript and Drs. Fred Asare and Frank Lee for kindly providing us with dasatinib. This research was supported by the Spanish Ministry of Economy and Competitiveness (SAF2010-18388, SAF2013-44677-R, and FIS PI12/00506), the SPANISH AIDS Research Network RD12/0017/0015 that is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER), Bristol-Myers Squibb (BMS AI471-041), joined program of the Agence nationale de recherches sur le sida et les hépatites virales (ANRS 2014-2), and the European FP7-HEALTH project HIT HIDDEN HIV. The work of E.M. is supported by Instituto de Salud Carlos III (MPY 1371/12). The work of B.D. is supported by the European FP7-HEALTH project HIT HIDDEN HIV. The ACTG study A5214 was supported by the NIH (AI 069501).es_ES
dc.language.isoenges_ES
dc.publisherElsevier es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshCD4-Positive T-Lymphocytes es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshHIV-1 es_ES
dc.subject.meshHumans es_ES
dc.subject.meshInterleukin-2 es_ES
dc.subject.meshInterleukin-7 es_ES
dc.subject.meshMonomeric GTP-Binding Proteins es_ES
dc.subject.meshPhosphorylation es_ES
dc.subject.meshProtein Processing, Post-Translational es_ES
dc.subject.meshReverse Transcription es_ES
dc.subject.meshSAM Domain and HD Domain-Containing Protein 1 es_ES
dc.subject.meshVirus Integration es_ES
dc.titleIL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cyclees_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID26923586es_ES
dc.format.volume14es_ES
dc.format.number9es_ES
dc.format.page2100-2107es_ES
dc.identifier.doi10.1016/j.celrep.2016.02.022es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderRed de Investigación Cooperativa en Investigación en Sida (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2211-1247es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2016.02.022es_ES
dc.identifier.journalCell reportses_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2010-18388es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-44677-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FIS PI12/00506es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BMS AI471-041es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ANRS 2014-2es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/MPY 1371/12es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/AI 069501es_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional