IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle.
IL-7 Induces SAMHD1 Phosphorylation in CD4+ T Lymphocytes, Improving Early Steps of HIV-1 Life Cycle.
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DOI：
10.1016/j.celrep.2016.02.022
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发表时间：
2016-03-08
期刊：
影响因子：
8.8
通讯作者：
Alcamí J
中科院分区：
文献类型：
--
作者：
Coiras M;Bermejo M;Descours B;Mateos E;García-Pérez J;López-Huertas MR;Lederman MM;Benkirane M;Alcamí J
HIV-1在CD 4+淋巴细胞中的整合后潜伏期是尽管治疗病毒持续存在的原因，但尚未完全了解建立潜伏病毒库的机制。我们确定，白细胞介素2（IL-2）和IL-7诱导SAMHD 1磷酸化T592，废除其抗病毒活性。然而，IL-7对HIV-1逆转录和整合的刺激作用比需要趋化因子共刺激的IL-2要深刻得多。由于NF-κB诱导较低，这两种细胞因子几乎不诱导转录，有利于建立潜伏性储库。在IL-7治疗的患者中证实了IL-7对SAMHD 1磷酸化的作用（ACTG 5214研究）。达沙替尼-a酪氨酸激酶通道阻断IL-2和IL-7诱导的SAMHD 1磷酸化，并恢复HIV-1限制。我们认为，γ c-细胞因子不仅通过驱动稳态增殖，而且通过SAMHD 1失活增加CD 4+淋巴细胞对HIV-1感染的易感性，在水库建立中发挥重要作用。Coiras等人表明IL-2和IL-7诱导SAMHD 1磷酸化，消除其抗病毒活性。这增加了CD 4+淋巴细胞对HIV-1感染的易感性，有助于建立储库。这些γ c-细胞因子还通过稳态增殖维持储库。酪氨酸激酶抑制剂达沙替尼阻断IL-2和IL-7诱导的SAMHD 1磷酸化，恢复HIV-1限制。
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. Coiras et al. show that IL-2 and IL-7 induce SAMHD1 phosphorylation, abrogating its antiviral activity. This increases susceptibility of CD4+ lymphocytes to HIV-1 infection, contributing to the establishment of the reservoir. These γc-cytokines also maintain the reservoir through homeostatic proliferation. The tyrosine-kinase inhibitor dasatinib blocked SAMHD1 phosphorylation induced by IL-2 and IL-7, restoring HIV-1 restriction.
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DOI：
10.1084/jem.20030735
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kondrack RM;Harbertson J;Tan JT;McBreen ME;Surh CD;Bradley LM
通讯作者：
Bradley LM
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Rosa Lopez-Huertas, Maria;Mateos, Elena;Coiras, Mayte
通讯作者：
Coiras, Mayte
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Ho YC;Shan L;Hosmane NN;Wang J;Laskey SB;Rosenbloom DI;Lai J;Blankson JN;Siliciano JD;Siliciano RF
通讯作者：
Siliciano RF