Alternative mechanisms for activation of human immunodeficiency virus enhancer in T cells.
Alternative mechanisms for activation of human immunodeficiency virus enhancer in T cells.
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DOI：
10.1126/science.2830675
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发表时间：
1988-03
期刊：
影响因子：
56.9
通讯作者：
Gary J. Nabel;Stephen A. Rice;D. Knipe;D. Baltimore
中科院分区：
文献类型：
--
作者：
Gary J. Nabel;Stephen A. Rice;D. Knipe;D. Baltimore
人类免疫缺陷病毒(HIV)在T细胞激活后的表达受核因子-kappa B的调节，核因子-kappa B是一种可诱导的DNA结合蛋白，可刺激转录。由各种DNA病毒编码的蛋白质也能够激活HIV增强子的表达。为了确定这种激活是如何发生的，已经确定了来自1型单纯疱疹病毒和腺病毒的特定基因，这些基因可以激活T淋巴瘤细胞中的艾滋病毒。HIV增强子中介导其作用的顺式作用调控序列也已被表征。相关基因是ICP0--1型单纯疱疹病毒的即刻早期产物--以及由腺病毒的13S信使RNA编码的E1a形式。腺病毒E1a对HIV的激活依赖于TATA盒，而疱疹病毒ICP0不通过单一的顺式作用元件发挥作用。这些发现表明，有多种途径可以绕过HIV的正常细胞激活，它们增加了这样一种可能性，即单纯疱疹病毒或腺病毒感染可能通过不依赖于T细胞抗原刺激的机制，直接促进获得性免疫缺陷综合征中HIV的激活。
The expression of human immunodeficiency virus (HIV) after T cell activation is regulated by NF-kappa B, an inducible DNA-binding protein that stimulates transcription. Proteins encoded by a variety of DNA viruses are also able to activate expression from the HIV enhancer. To determine how this activation occurs, specific genes from herpes simplex virus type 1 and adenovirus that activate HIV in T lymphoma cells have been identified. The cis-acting regulatory sequences in the HIV enhancer that mediate their effect have also been characterized. The relevant genes are those for ICP0-an immediate-early product of herpes simplex virus type 1-and the form of E1A encoded by the 13S messenger RNA of adenovirus. Activation of HIV by adenovirus E1A was found to depend on the TATA box, whereas herpesvirus ICP0 did not work through a single defined cis-acting element. These findings suggest multiple pathways that can be used to bypass normal cellular activation of HIV, and they raise the possibility that infection by herpes simplex virus or adenovirus may directly contribute to the activation of HIV in acquired immunodeficiency syndrome by mechanisms independent of antigenic stimulation in T cells.