Drugs of Abuse Affecting AIDS Pathogenesis

影响艾滋病发病机制的滥用药物

• 批准号: 7647929
• 负责人: Thomas J Rogers
• 金额: $ 156万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647929
• 关键词: Drugs; Abuse; Affecting; AIDS; Pathogenesis

DESCRIPTION (provided by the applicant): In the United States, approximately 33% of individuals who are infected by the Human Immunodeficiency Virus (HIV) are intravenous drug abusers. Current evidence suggests that opioid abuse may promote the disease that occurs following this infection. We believe that the issue of the precise nature of the influence of opioid drugs of abuse in the development of HIV encephalitis is a critical question which remains largely unanswered. In this Program Project application, we propose four projects which will clarify the role of opioid abuse in the development of this disease process. Project 1 will address the combined influence of morphine and SIV infection on the expression of critical chemokines and chemokine receptors that play an important role in the development of SIV encephalitis. We will investigate the impact of both chronic morphine administration on expression of these crucial cytokines and their receptors at both the cellular and molecular level. Project 2 will investigate the effect of morphine on the pathogenesis of SIV infection in rhesus macaques. We will investigate the effect of viral load, immunophenotype of immune cells, and investigate the effect of drug treatment on the trafficking of infected cells into the CNS, lymph nodes, and other organs. Project 3 addresses the issue of the neuropathogenesis that is caused by a direct pathway that includes infection of macrophages, microglia, and astrocytes in the CNS, and an indirect pathway that involves dysregulation of immunomodulators and cytokines, and their downstream signaling pathways by viral proteins, such as gp120 and Tat, in both infected and uninfected bystander cells including neurons. In this research project we will focus our attention on a cytokine which has been implicated in direct and indirect pathways, and we will examine the effect of morphine on HIV-1 gene expression and replication, neuronal cell function, and apoptosis. Project 4 seeks to examine alterations in immune parameters following administration of morphine in both SIV-infected and non-infected macaques. An assessment of the immunological competence of animals in each treatment/infection group will be determined. Studies will include an analysis of the competence of both the acquired and innate immune systems. This application also includes administrative, animal, flow cytometry, and immunohistopathology cores to support the four research projects. PROGRAM PROJECT CHARACTERISTICS

描述（由申请人提供）：在美国，被人类免疫缺陷病毒感染（HIV）感染的个体中约有33％是静脉滥用者。 当前的证据表明，阿片类药物滥用可能会促进这种感染后发生的疾病。 我们认为，阿片类药物滥用药物在艾滋病毒脑炎发展中的影响的确切性质的问题是一个关键问题，在很大程度上尚未得到答复。 在此计划项目应用程序中，我们提出了四个项目，这些项目将阐明阿片类药物在此疾病过程中的作用。 项目1将解决吗啡和SIV感染对关键趋化因子和趋化因子受体表达的综合影响，这些因子和趋化因子受体在SIV脑炎的发展中起着重要作用。 我们将研究慢性吗啡给予这些关键细胞因子及其受体在细胞和分子水平上的表达的影响。 项目2将研究吗啡对恒河猕猴中SIV感染的发病机理的影响。 我们将研究病毒载量，免疫细胞免疫表型的影响，并研究药物治疗对被感染细胞运输到中枢神经系统，淋巴结和其他器官的影响。 项目3解决了由直接途径引起的神经病生成问题，该途径包括CNS中巨噬细胞，小胶质细胞和星形胶质细胞的感染以及与免疫调节剂和细胞因子的失调及其在gpp120中受感染蛋白的下游信号通路的间接途径，该途径涉及免疫调节剂和细胞的失调，以及其下游信号的途径，以及gpp120和Tats in in in toce and gpp120 and Introf Introf Introf Introf Introved and Intof Trounty toctorect。神经元。 在该研究项目中，我们将注意力集中在与直接和间接途径有关的细胞因子上，我们将研究吗啡对HIV-1基因表达和复制，神经元细胞功能和凋亡的影响。 项目4旨在检查在SIV感染和未感染的猕猴中给出吗啡后免疫参数的变化。 将确定每个治疗/感染组中动物的免疫能力的评估。 研究将包括对获得和先天免疫系统的能力的分析。 该应用程序还包括行政，动物，流式细胞仪和免疫组织病理学核心，以支持这四个研究项目。 计划项目特征