ALCOHOL, HIV1 PROTEINS AND IMMUNOSUPPRESSION

酒精、HIV1 蛋白和免疫抑制

• 批准号: 2769240
• 负责人: OM PRAKASH
• 金额: $ 9.31万
• 依托单位: OCHSNER CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-25 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769240
• 关键词: alcoholic beverage consumption; alcohols; antioxidants; apoptosis; cytokine; cytotoxic T lymphocyte; genetically modified animals; host organism interaction; human immunodeficiency virus 1; immunopharmacology; immunosuppression; laboratory mouse; natural killer cells; tissue /cell culture; virus protein

APPLICANT'S ABSTRACT: Immunosuppression resulting from human immunodeficiency virus (HIV) infection and alcohol abuse are common in the U.S. population and frequently coexist in the same individual. Currently, there is little information on how these two immunosuppressive states might interact with each other to alter host defense mechanisms. Preliminary studies have shown that a number of immune functions are compromised in mice transgenic for the HIV-1 Tat protein. There is also evidence that other HIV-encoded proteins contribute to immunosuppression and immune dysfunctions. It is our hypothesis that alcohol can function as a cofactor with HIV-encoded proteins to further compromise host immune functions and increase host susceptibility to disease progression. This proposal will test this hypothesis in transgenic mice that express Tat (Tat86) protein and HIV mice that express HIV-encoded proteins from a gag-pol defective proviral DNA, and has 3 Specific Aims. Specific Aim 1 to determine the effect of alcohol and HIV proteins on T cell numbers and mechanism of T cell loss. Tat and HIV mice will be exposed to alcohol (20% w/v) in drinking water from 2 to 8 weeks. T cell numbers in thymus and spleen tissues of these animals will be compared to those from alcohol-treated nontransgenic littermates every 2 weeks. Animals in each group without alcohol treatment will serve as controls. We will also focus on expression of cellular factors that are associated with apoptotic mechanisms. Since HIV infection is associated with oxidative stress and Tat itself is known to contribute to it, in Specific Aim 2, we will assess the contribution of alcohol on antioxidant defenses by measuring parameters associated with oxidative stress. In Specific Aim 3, we will compare the immune functions of splenic lymphocytes from alcohol-treated and -untreated mice. Planned experiments will focus on: 1) Cytotoxic T lymphocyte function; 2) Natural killer cell function; and 3) Release of TH1 and TH2 cell-specific cytokines. Information gained from this exploratory project may enhance our understanding of alcohol as a cofactor in HIV pathogenesis and open new avenues of research.

申请人摘要：人体免疫抑制 免疫缺陷病毒（艾滋病毒）感染和酗酒是常见的， 美国在同一个人身上，经常会出现同一个人。 目前， 关于这两种免疫抑制状态如何 相互作用改变宿主的防御机制 初步 研究表明，小鼠的许多免疫功能受到损害， HIV-1达特蛋白的转基因。 也有证据表明， HIV编码的蛋白质有助于免疫抑制和免疫应答。 功能障碍 我们的假设是酒精可以作为一种辅助因子 与HIV编码的蛋白质进一步损害宿主的免疫功能， 增加宿主对疾病进展易感性。 这项提议将在表达达特的转基因小鼠中检验这一假设 （Tat 86）蛋白和表达来自一种病毒的HIV编码蛋白的HIV小鼠。 gag-pol缺陷的前病毒DNA，并具有3个特异性目的。 具体目标1至 确定酒精和HIV蛋白对T细胞数量的影响， T细胞丢失的机制。 达特和HIV小鼠将暴露于酒精（20%）中， w/v）在饮用水中2 - 8周。 胸腺中的T细胞数量和 这些动物的脾组织将与来自 酒精处理的非转基因同窝仔每2周。 只动物 未用酒精处理的组作为对照。 我们还将重点 与细胞凋亡相关的细胞因子的表达 机制等 由于HIV感染与氧化应激和达特有关， 在具体目标2中，我们将评估 通过测量参数确定酒精对抗氧化防御的作用 与氧化应激有关。 在具体目标3中，我们将比较 酒精处理与未处理小鼠脾淋巴细胞免疫功能的比较 小鼠 计划的实验将集中在：1）细胞毒性T淋巴细胞 功能; 2）自然杀伤细胞功能;和3）TH 1和TH 2的释放 细胞特异性细胞因子。 从这个探索性项目中获得的信息可能会提高我们的 了解酒精作为艾滋病发病机制的辅助因子，并开辟新的 研究的途径。