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

TitleIL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle.
Publication TypeJournal Article
Year of Publication2016
AuthorsCoiras M, Bermejo M, Descours B, Mateos E, García-Pérez J, López-Huertas M-R, Lederman MM, Benkirane M, Alcamí J
JournalCell Rep
Volume14
Issue9
Pagination2100-2107
Date Published2016 Mar 08
ISSN2211-1247
KeywordsCD4-Positive T-Lymphocytes, Cells, Cultured, HIV-1, Humans, Interleukin-2, Interleukin-7, Monomeric GTP-Binding Proteins, Phosphorylation, Protein Processing, Post-Translational, Reverse Transcription, SAM Domain and HD Domain-Containing Protein 1, Virus Integration
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.

DOI10.1016/j.celrep.2016.02.022
Alternate JournalCell Rep
PubMed ID26923586
PubMed Central IDPMC5063304
Grant ListP30 AI036219 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
AI 069501 / AI / NIAID NIH HHS / United States