Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells
Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells
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DOI：
10.1182/blood-2008-07-168393
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发表时间：
2009-01-01
期刊：
影响因子：
20.3
通讯作者：
Planelles, Vicente
中科院分区：
文献类型：
--
作者：
Bosque, Alberto;Planelles, Vicente
在1型人类免疫缺陷病毒（HIV - 1）感染患者中使用抗逆转录病毒疗法无法根除病毒。这在很大程度上是因为HIV - 1能够建立一个高度稳定的潜伏感染细胞储存库。在这项研究中，我们描述了一种体外实验系统，该系统利用原代CD4(+) T细胞产生高水平的HIV - 1潜伏感染记忆细胞。利用这个模型，我们能够剖析T细胞信号通路，并对记忆CD4(+) T细胞中HIV - 1重新激活所涉及的长末端重复序列（LTR）顺式作用元件进行表征。我们得出结论，在记忆T细胞中，最佳的潜伏病毒重新激活需要Lck和活化T细胞的核因子（NFAT），但不需要NF - κB。我们还发现，对HIV - 1重新激活至关重要的顺式作用元件是Sp1和κB/NFAT转录因子结合位点。（《血液》2009年；113卷：58 - 65页）
The use of antiretroviral therapy in HIV type 1 (HIV-1) -infected patients does not lead to virus eradication. This is due, to a significant degree, to the fact that HIV-1 can establish a highly stable reservoir of latently infected cells. In this work, we describe an ex vivo experimental system that generates high levels of HIV-1 latently Introduction infected memory cells using primary CD4(+) T cells. Using this model, we were able to dissect the T cell-signaling pathways and to characterize the long terminal repeat (LTR) cis-acting elements involved in reactivation of HIV-1 in memory CD4(+) T cells. We conclude that Lck and nuclear factor of activated T cells (NFAT), but not NF-kappa B, are required for optimal latent virus reactivation in memory T cells. We also found that the cis-acting elements which are critical toward HIV-1 reactivation are the Sp1 and kappa B/NFAT transcription factor binding sites. (Blood. 2009; 113: 58-65)