Nabel G J, Rice S A, Knipe D M, Baltimore D
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Science. 1988 Mar 11;239(4845):1299-302. doi: 10.1126/science.2830675.
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.
人类免疫缺陷病毒（HIV）在T细胞激活后的表达受核因子κB（NF-κB）调控，NF-κB是一种可诱导的DNA结合蛋白，能刺激转录。多种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，已经在T淋巴瘤细胞中鉴定出了来自1型单纯疱疹病毒和腺病毒的、可激活HIV的特定基因。HIV增强子中介导其效应的顺式作用调控序列也已得到表征。相关基因是1型单纯疱疹病毒的即刻早期产物ICP0的基因，以及腺病毒13S信使RNA编码的E1A形式的基因。发现腺病毒E1A对HIV的激活依赖于TATA框，而疱疹病毒ICP0并非通过单一确定的顺式作用元件发挥作用。这些发现提示了多种可用于绕过HIV正常细胞激活的途径，并且增加了一种可能性，即单纯疱疹病毒或腺病毒感染可能通过独立于T细胞抗原刺激的机制，直接促成获得性免疫缺陷综合征中HIV的激活。
