COMPLEMENT INTERACTION WITH HIV AND HIV-INFECTED CELLS

补充与 HIV 和 HIV 感染细胞的相互作用

• 批准号: 3144544
• 负责人: GREGORY T SPEAR
• 金额: $ 15.52万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3144544
• 关键词: AIDS; antibody specificity; cell mediated cytotoxicity; chromium; complement; complement pathway; complement receptor; flow cytometry; genetic strain; helper T lymphocyte; host organism interaction; human immunodeficiency virus; human subject; macrophage; natural killer cells; nucleic acid hybridization; polymerase chain reaction; provirus; radiotracer; tissue /cell culture; trypan blue; virus antigen

The overall goal of this proposal is to develop an understanding of the interaction of complement-receptor expressing cells with either complement-treated HIV-infected cells or complement-treated HIV. After infection with HIV, cells express viral proteins on their surface which can lead to cell-surface deposition of complement breakdown products. Since many immune effector cells express receptors for-these complement breakdown products, the complement activation by infected cells could potentially have a great impact on infected cell survival or function. Cells that express complement receptors may also interact differently with HIV after it is exposed to complement; HIV can also potentially activate complement in vivo. The recent discovery that some CD4+ cells express complement receptors (CR2) suggests that this subset could be infected more easily by virus that bears complement-breakdown products on its surface. To address these problems, we specifically propose to; 1. Determine the ability of HIV-infected cells to activate complement. The complement pathway(s) by which complement is activated and requirements for cell type, virus strain and specific antibody will be assessed. Flow cytometric methods will be used. 2. Study the result of complement activation by HIV-infected cells on their destruction by complement-receptor positive effector cells. Macrophages, NK cells, and cells which mediate ADCC will be evaluated for complement-enhanced killing of infected targets. 51Cr-release, trypan blue and propidium iodide cytotoxic assays will be used to assess killing. 3.Determine the effect of complement activation by HIV on tropism for complement receptor positive cells. We will focus on the interaction of HIV with the recently described CR2+CD4+ subset of lymphocytes. Flow cytometric sorting and in vitro infection of uninfected cells will be performed. Possible in vivo infection of these cells will be assessed by obtaining them from infected persons and flow cytometrically analyzing and sorting to obtain subsets followed by HIV provirus DNA quatitation. The studies proposed here will help gain knowledge of the interaction between complement and HIV. An understanding of this interaction may enable the design of drugs or vaccine strategies which will bolster or supplement the ability of oomplement to benefit the infected person while avoiding any harmful effects.

该提议的总体目标是建立对 补体受体表达细胞的相互作用与任何一个 补体治疗的HIV感染细胞或补体治疗的HIV。 感染HIV后，细胞在其表面表达病毒蛋白 这可能导致补体分解产物的细胞表面沉积。 由于许多免疫效应细胞表达这些补体的受体 分解产物，被感染细胞的补体激活可以 可能对感染的细胞存活或功能有很大的影响。 表达补体受体的细胞也可能与 艾滋病毒暴露于补充后；艾滋病毒也可能激活 补充体内。 最近发现某些CD4+细胞表达的发现 补体受体（CR2）表明该子集可能会被更多地感染 通过在其表面上带有补体破坏产品的病毒很容易。 为了解决这些问题，我们特别建议； 1。确定感染HIV的细胞激活补体的能力。 这 补体的补充途径被激活，并要求 将评估细胞类型，病毒菌株和特异性抗体。 流动 将使用细胞仪方法。 2。研究艾滋病毒感染细胞对其补体激活的结果 补体受体阳性效应细胞的破坏。 巨噬细胞， NK细胞和介导ADCC的细胞将被评估 补体增强的杀害感染靶标。 51克释放，锥蓝色 碘化丙肽细胞毒性测定将用于评估杀戮。 3.确定艾滋病毒补体激活对嗜性的影响 补体受体阳性细胞。 我们将专注于互动 HIV具有最近描述的CR2+ CD4+子集的淋巴细胞。 流动 未感染细胞的细胞仪分选和体外感染将是 执行。 这些细胞的体内感染可能会通过 从受感染的人和流式的细胞学分析中获取它们，并 排序以获取子集，然后进行HIV病毒DNA平流。 这里提出的研究将有助于了解互动 在补充和艾滋病毒之间。 对这种互动的理解可能 启用可以加强或 补充O配合使受感染者受益的能力 避免任何有害影响。