Modalities of interleukin-7-induced human immunodeficiency virus permissiveness in quiescent T lymphocytes
Modalities of interleukin-7-induced human immunodeficiency virus permissiveness in quiescent T lymphocytes
复制标题
DOI：
10.1128/jvi.76.18.9103-9111.2002
复制
发表时间：
2002-09-01
影响因子：
5.4
通讯作者：
Trono, D
中科院分区：
文献类型：
--
作者：
Ducrey-Rundquist, O;Guyader, M;Trono, D
原代T淋巴细胞的代谢和细胞周期状态决定了它们对人类免疫缺陷病毒（HIV）和HIV衍生载体的易感性。虽然在完全静止的T淋巴细胞中，这些逆转录因子的逆转录和核输入受损，导致感染失败，但各种刺激可以诱导病毒的容许状态。在这里，我们研究了白细胞介素-7（IL-7），T细胞稳态的重要控制器，发挥这种作用的方式。IL-7暴露的脐带血T淋巴细胞增殖，并有效地转导HIV衍生的载体。相比之下，类似处理的成人外周血（PB）T淋巴细胞不能分裂，只有这些细胞的一个子集变得可感染。IL-7处理的PB T淋巴细胞的HIV抗性和敏感性亚群在细胞周期状态上不同，但在幼稚、记忆或活化表型上不同。IL-7不能诱导活化T细胞的核因子，环孢素不能阻止HIV介导的基因转移。此外，磷脂酰肌醇3-激酶（PI 3 K）抑制剂渥曼青霉素阻断IL-7诱导的细胞存活和Bcl-2合成，但对HIV易感性的获得没有影响，这表明IL-7诱导的HIV 1型容许性不是由PI-3 K途径介导的，并且可能是Jak/STAT 5途径（IL-7触发的T细胞信号传导的另一种已知介质）控制这一过程。
The metabolic and cell cycle status of primary T lymphocytes conditions their susceptibility to human immunodeficiency virus (HIV) and HIV-derived vectors. While in fully quiescent T lymphocytes the reverse transcription and nuclear import of these retroelements are impaired, leading to an abortive infection, various stimuli can induce a state of virus permissiveness. Here, we studied the modalities by which interleukin-7 (IL-7), an important controller of T-cell homeostasis, exerts this effect. IL-7-exposed cord blood T lymphocytes proliferated and were efficiently transduced by HIV-derived vectors. In contrast, similarly treated adult peripheral blood (PB) T lymphocytes failed to divide, and only a subset of these cells became infectible. HIV-resistant and -sensitive subsets of IL-7-treated PB T lymphocytes differed in cell cycle status but not in naive, memory, or activation phenotypes. Nuclear factor of activated T cells was not induced by IL-7, and cyclosporine did not prevent HIV-mediated gene transfer. Furthermore, the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin blocked IL-7-induced cell survival and Bcl-2 synthesis but had no effect on the acquisition of HIV susceptibility, suggesting that IL-7-induced HIV type 1 permissiveness is not mediated by the PI-3 K pathway and that, perhaps, the Jak/STAT5 pathway, the other known mediator of IL-7-triggered signaling in T cells, governs this process.