REGULATION OF HIV-1 GENE EXPRESSION IN HUMAN T-CELLS AND MACROPHAGES

我们继续研究艾滋病毒基因表达的调控， HIV感染对细胞基因表达的影响。我们专注于 最近的努力，确定分子机制， 病毒反式激活LTR中的HIV基因调节区。DNA 已经鉴定了对ICPO HSV早期蛋白有反应的结合位点 并定义了启动子和增强子位点的层次结构， NF κ B、AP-2、SP-1和TATA结合位点。HSV反式激活涉及 广义细胞激活级联反应，可以修改和激活 多个DNA结合蛋白，从而启动HIV基因表达。我们 还定义了另一种细胞DNA结合蛋白复合物， 似乎与特定的DNA结合蛋白相结合， 转录活性前病毒染色体区域。这种蛋白质复合物 有趣的是，它也是许多自身免疫性疾病中的自身抗原。 系统性红斑狼疮和硬皮病。 我们继续研究艾滋病毒在激活细胞基因方面的作用。 我们与牙科研究所的弗朗西斯博士合作， HIV可以激活核DNA结合蛋白， 产生多种细胞因子，包括TNF和IL-1。我们 目前正在研究这种诱导途径的机制， 与疱疹早期使用的反式激活机制有关， proteins.

We have continued studies on the regulation of HIV gene expression and the effects of HIV infection on cellular gene expression. We have focused our more recent efforts on defining the molecular mechanism by which herpes viruses transactivate the HIV gene regulatory regions in the LTR. DNA binding sites responsive to the ICPO HSV early protein have been identified and define a heirarchy of promoter and enhancer sites which include the NFKB, AP-2, SP-1 and TATA binding sites. HSV transactivation involves a generalized cellular activation cascade which can modify and activate multiple DNA-binding proteins thereby initiating HIV gene expression. We have also defined another cellular DNA-binding protein complex which appears to associate with specific DNA-binding proteins to stabilize transcriptionally active proviral chromosomal regions. This protein complex is interesting in that it is also an autoantigen in a number of autoimmune diseases such as systemic lupus erythematosis and scleroderma. We have continued studies on the role of HIV in activating cellular genes. In collaboration with Dr. Francis at the Dental Institute, we have found that HIV can activate nuclear DNA-binding proteins to initiate the production of a variety of cytokines including TNF and IL-1. We are currently studying the mechanism for this induction pathway, which appears to be related to the transactivation mechanisms used by the herpes early proteins.