Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Purα

JC virus is activated to replicate in glial cells of many AIDS patients with neurological disorders. In human glial cells, the human immunodeficiency virus 1 (HIV-1) Tat protein activates the major late promoter of JC virus through a Tat-responsive DNA element, termed upTAR, which is a recognition site for cellular Purα, a sequence-specific single-stranded DNA binding protein implicated in cell cycle control of DNA replication and transcription. Tat interacts with two leucine-rich repeats in Purα to form a complex that can be immunoprecipitated from cell extracts. Tat enhances the ability of purified glutathione S-transferase-Purα (GST-Purα) to bind the upTAR element. Tat acts synergistically with Purα, in a cell-cycle-dependent manner, to activate transcription at an upTAR element placed upstream of a heterologous promoter. Since Purα is ubiquitously expressed in human cells and since PUR elements are located near many promoters and origins of replication, the Tat-Purα interaction may be implicated in effects of HIV-1 throughout the full range of HIV-1-infected cells.

JC病毒（JC virus）可在众多伴随神经系统疾病的艾滋病患者的神经胶质细胞中被激活并复制。在人类神经胶质细胞内，人类免疫缺陷病毒1型（HIV-1）的Tat蛋白（Tat protein）通过一个被命名为upTAR的Tat响应DNA元件，激活JC病毒的主要晚期启动子；该upTAR元件是细胞源性Purα（Purα）的识别位点，而Purα是一种参与DNA复制与转录细胞周期调控的序列特异性单链DNA结合蛋白。Tat与Purα内的两处富亮氨酸重复序列相互作用，形成可从细胞提取物中免疫沉淀的复合物。Tat可增强纯化的谷胱甘肽S-转移酶-Purα（GST-Purα）结合upTAR元件的能力。Tat可与Purα以细胞周期依赖性方式协同作用，在置于异源启动子上游的upTAR元件处激活转录。鉴于Purα在人类细胞中广谱表达，且PUR元件位于众多启动子和复制起始位点附近，Tat-Purα相互作用可能与HIV-1在所有受HIV-1感染的细胞类型中产生的效应相关。