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Drugs of Abuse Affecting AIDS Pathogenesis

影响艾滋病发病机制的滥用药物

基本信息

批准号：
8261935
负责人：
Thomas J Rogers
金额：
$ 118.06万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8261935
关键词：
AIDS neuropathy Acquired Immunodeficiency Syndrome Address Affect Animal Model Animals Apoptosis Area Astrocytes Attention Biological Models CCL2 gene Caring Cell Line Cell physiology Cells Characteristics Chronic Chronic Phase Clinical Collaborations Competence Confounding Factors (Epidemiology)Control Groups Country Data Development Disease Divorce Dose Drug abuse Encephalitis Environment Epidemiologic Studies Epidemiology Equilibrium Event Exposure to Flow Cytometry Frequencies Gene Expression Gene Expression Regulation HIV HIV Envelope Protein gp120 HIV encephalitis HIV-1 Haplotypes Heroin Histopathology Human Immune Immune response Immune system Immunocompetence Immunologist Immunomodulators Immunophenotyping Immunosuppression Immunosuppressive Agents In Vitro Incidence Individual Infection Inflammatory Intravenous Laboratory Study Leukocytes Ligands Macaca Macaca mulatta Major Histocompatibility Complex Malnutrition Matched Group Methodology Microglia Modeling Molecular Monkeys Morphine Nature Needle Sharing Neurologic Neurons Neuropathogenesis Opiates Opioid Opioid Receptor Organ Parasites Pathogenesis Pathway interactions Pharmaceutical Preparations Pharmacology Pilot Projects Plague Play Population Positioning Attribute Predisposition Process Production Program Research Project Grants Proteins Protocols documentation Publishing RANTES Randomized Regulation Regulatory T-Lymphocyte Relative (related person)Reporting Research Research Design Research Personnel Research Project Grants Resistance Role SIV Saline Signal Pathway Signaling Protein Suggestion Testing Time Transcription Regulatory Protein United States Universities Ursidae Family Viral Viral Load result Viral Proteins Virus Virus Diseases Virus Replication Withdrawal Work base chemokine chemokine receptor cytokine design drug abuser drug of abuse experience high risk behavior improved in vivo interest intravenous injection lymph nodes macrophage monocyte nervous system disorder neuropathology nonhuman primate opioid abuse opioid withdrawal p65 programs receptor receptor expression response tool trafficking transmission process

项目摘要

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，大约33%的人类免疫缺陷病毒（HIV）感染者是静脉注射药物滥用者。目前的证据表明，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，阿片类药物滥用对艾滋病毒脑炎发展的影响的确切性质是一个关键问题，在很大程度上仍然没有答案。在这个项目申请中，我们提出了四个项目，将阐明阿片类药物滥用在这种疾病发展过程中的作用。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联合影响，这些趋化因子和趋化因子受体在SIV脑炎的发展中起重要作用。我们将研究慢性吗啡给药对这些关键细胞因子及其受体在细胞和分子水平表达的影响。项目2将研究吗啡对恒河猴SIV感染发病机制的影响。我们将研究病毒载量的影响，免疫细胞的免疫表型，并研究药物治疗对感染细胞进入CNS，淋巴结和其他器官的影响。项目3解决了由直接途径（包括CNS中巨噬细胞、小胶质细胞和星形胶质细胞的感染）和间接途径（涉及免疫调节剂和细胞因子的失调）以及病毒蛋白（如gp 120和达特）在感染和未感染的旁观者细胞（包括神经元）中的下游信号传导途径引起的神经发病机制问题。在这个研究项目中，我们将把我们的注意力集中在直接和间接途径中涉及的细胞因子上，我们将研究吗啡对HIV-1基因表达和复制、神经细胞功能和凋亡的影响。项目4旨在研究SIV感染和未感染猕猴给予吗啡后免疫参数的变化。将确定每个处理/感染组动物的免疫能力评估。研究将包括对获得性和先天免疫系统能力的分析。该应用程序还包括行政，动物，流式细胞术和免疫组织病理学核心，以支持四个研究项目。项目特点