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Cell Rep. 2016 Mar 8;14(9):2100-2107. doi: 10.1016/j.celrep.2016.02.022. Epub 2016 Feb 25.

IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle.

Author information

1
AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain. Electronic address: mcoiras@isciii.es.
2
AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain.
3
Institut de Génétique Humaine CNRS UPR1142, Université de Montpellier, Laboratoire de Virologie Moléculaire, Montpellier 34000, France.
4
Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
5
AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid 28220, Spain. Electronic address: ppalcami@isciii.es.

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.

PMID:
26923586
PMCID:
PMC5063304
DOI:
10.1016/j.celrep.2016.02.022
[Indexed for MEDLINE]
Free PMC Article

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