STEROID HORMONES, HIV-INFECTED CELLS AND HIV GENES

类固醇激素、HIV 感染细胞和 HIV 基因

• 批准号: 3241641
• 负责人: E B THOMPSON
• 金额: $ 15.11万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-02-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241641
• 关键词: AIDS; CD4 molecule; HIV infections; Herpesviridae disease; cell bank /registry; clone cells; cytolysis; estrogens; gene expression; glucocorticoids; hormone receptor; human immunodeficiency virus; human tissue; messenger RNA; molecular pathology; mouse mammary tumor virus; nuclear magnetic resonance spectroscopy; peptide hormone biosynthesis; progestins; ribosomal RNA; steroid hormone; transfection; transposon /insertion element; virus cytopathogenic effect; virus genetics

This project is designed to do two things: first, to test the hypothesis that changes in steroid hormone effects are involved in the direct and indirect cytopathicity of HIV; and second, to use a DNA response element for glucocorticoids as a cis-active control over HIV genes to determine their functions quantitatively. Steroid hormones have profound effects on lymphoid cells directly and also indirectly, through influences on many peptide hormones and their receptors. We will investigate the effects of steroids on peripheral blood lymphoid cells of HIV infected individuals and on several infected cell lines. This will require studies of cellular effects of steroids, analysis of steroid receptors, and examination of the interactive effects of steroids with several peptide hormones and their receptors. Limited reports raise the possibility that HIV is glucocorticoid-inducible. We will thoroughly test this possibility. The exact function of several HIV genes is unknown, as are the quantitative relationships between specific gene products and overall HIV replication and cytopathicity. We will place the glucocorticoid response element from the MMTV LTR in a cis relationship to HIV or specific HIV genes, to provide glucocorticoid-regulatable HIV genes for study in transfected cells. Our clonal lines of CEM cells with known lesions in the glucocorticoid response system, should be of particular value in these studies.

该项目旨在做两件事：首先，测试 假设类固醇激素作用的变化涉及 艾滋病毒的直接和间接细胞病变；其次，使用 糖皮质激素作为顺式对照的DNA响应元件 超过艾滋病毒基因以定量确定其功能。 类固醇激素对淋巴样细胞具有深远的作用 并间接地通过对许多肽激素的影响 和他们的受体。 我们将研究类固醇的影响 在HIV感染个体的外​​周血淋巴样细胞上 在几个感染的细胞系上。 这将需要研究 类固醇的细胞作用，类固醇受体的分析和 检查类固醇与几种类固醇的互动作用 肽激素及其受体。 有限的报告提出了 HIV可能是糖皮质激素诱导的可能性。 我们将 彻底测试这种可能性。 几个HIV基因的确切功能尚不清楚， 特定基因产品与 总体艾滋病毒复制和细胞病变。 我们将放置 来自顺式MMTV LTR的糖皮质激素反应元件 与艾滋病毒或特定的艾滋病毒基因的关系，以提供 糖皮质激素可调节的HIV基因，用于转染的研究 细胞。 我们在CEM细胞中具有已知病变的克隆线 糖皮质激素反应系统应在 这些研究。