PDF(Pubmed)
Abstract：
HIV-1 infection leads to a gradual loss of T helper cells, chronic immune activation, and eventual immune system breakdown. HIV-1 causes deregulation of the expression of IL-2, a cytokine important for T helper cell growth and survival, which is downregulated in HIV-1 patients. The present study addresses the regulation of IL2 expression via HIV-1 Tat transcriptional activator. We used J-LAT cells, a T cell line that serves as a latency model for studies of HIV-1 expression in T cells, and as controls a T cell line lacking HIV-1 elements and a T cell line with a stably integrated copy of the HIV-1-LTR promoter. We show that endogenously expressed Tat inhibits IL2 transcription in J-Lat cells via its presence in the ARRE-1/2 elements of the IL2 promoter and that the inhibition of IL2 expression is mediated by Tat inhibiting Pol II activity at the IL2 promoter, which is mediated by preventing the presence of Pol II at the ARRE-1/2 elements. Overall, Tat is present at the IL2 promoter, apart from its cognate HIV-1 LTR target. This supports our current knowledge of how HIV-1 affects the host transcriptional machinery and reflects the potential of Tat to disrupt transcriptional regulation of host genes to manipulate cell responses.
摘要：
HIV-1感染导致T辅助细胞逐渐丧失，慢性免疫激活，和最终的免疫系统崩溃。HIV-1导致IL-2的表达失调，IL-2是T辅助细胞生长和存活的重要细胞因子，在HIV-1患者中下调。本研究致力于通过HIV-1Tat转录激活因子调节IL2表达。我们用了J-LAT细胞,作为研究HIV-1在T细胞中表达的潜伏期模型的T细胞系，以及作为对照的缺乏HIV-1元件的T细胞系和具有HIV-1-LTR启动子的稳定整合拷贝的T细胞系。我们表明，内源性表达的Tat通过其在IL2启动子的ARRE-1/2元件中的存在来抑制J-Lat细胞中的IL2转录，并且IL2表达的抑制是由Tat抑制IL2启动子上的PolII活性介导的。这是通过防止在ARRE-1/2元件上存在PolII来介导的。总的来说,Tat存在于IL2启动子，除了其同源的HIV-1LTR目标。这支持了我们目前关于HIV-1如何影响宿主转录机制的知识，并反映了Tat破坏宿主基因转录调节以操纵细胞反应的潜力。
