HIV PROJECT

艾滋病项目

• 批准号: 8365479
• 负责人: RICHARD D SMITH
• 金额: $ 10.36万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365479
• 关键词: Acquired Immunodeficiency Syndrome; Biological Assay; Biology; Brain Injuries; Buprenorphine; Cerebrospinal Fluid; Complex; Data; Disease Progression; Event; Funding; Genetic; Grant; HIV-1; Heroin; Human; Immunologics; Individual; Infection; Mass Spectrum Analysis; Modeling; National Center for Research Resources; Neurologic; Opioid; Pathogenesis; Pathologic; Pathology; Principal Investigator; Protease Inhibitor; Proteins; Proteome; Proteomics; Research; Research Infrastructure; Research Personnel; Resolution; Resources; SIV; Sampling; Source; Substance abuse problem; Techniques; Technology; United States National Institutes of Health; Virus Diseases; biosignature; cost; experience; immune activation; nonhuman primate; response; therapy design

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We plan to establish a Pilot Proteomics Center that will apply powerful new proteomics technologies to broadly investigate changes in protein abundances resulting from the pathologic events associated with concomitant lentiviral infection and substance abuse as well as from pharmacologic interventions designed to treat these pathologies. These complex interactions will be studied in human immunodeficiency virus, type 1 (HIV)-infected and -uninfected subjects, treated or not with exogenous opioids as well as in well-defined nonhuman primate models of lentiviral pathogenesis induced by the simian immunodeficiency virus (SIV). In so doing, we aim to identify the quantitative proteomic biosignatures and profiles that define and predict the impact of opioids on lentiviral disease progression, with particular emphasis on the neurological sequelae that accompany the acquired immune deficiency syndrome (AIDS). These efforts will benefit from execution in a manner that benefits from the extensive experience of the investigators, existing sample sets, comparison of human and non-human primate responses, and the extensive use of complementary data and techniques (e.g. immunologic and microarray assays). Through utilizing PNNL's experience and expertise in mass spectrometry for proteomic applications, the Proteomics Core will use high-resolution separations and mass spectrometry to support the following three projects. Project 1: To use high-throughput proteomics to define changes in the cerebrospinal fluid (CSF) proteome in HIV infection related to brain injury, intrathecal immune activation, CNS infection, and opioid use. Project 2: To explore the effect of opioids on the proteomic, immunologic, and genetic, signatures of non-human primates (NHP) that are uninfected or that have pathogenic or non-pathogenic SIV infection. Project 3: To evaluate the immunomodulatory effects of heroin, buprenorphine, and protease inhibitors in opioid-dependent individuals, infected or not with HIV.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们计划建立一个试点蛋白质组学中心，该中心将应用强大的新蛋白质组学技术来广泛调查与伴随的慢病毒感染和药物滥用相关的病理事件以及旨在治疗这些病理的药物干预所导致的蛋白质丰度的变化。这些复杂的相互作用将在人类免疫缺陷病毒、1型(HIV)感染和未感染的受试者中进行研究，无论是否使用外源性阿片类药物治疗，以及由猴免疫缺陷病毒(SIV)诱导的明确的非人类灵长类动物慢病毒致病模型。在这样做的过程中，我们的目标是确定定义和预测阿片类药物对慢病毒疾病进展的影响的定量蛋白质组生物签名和图谱，特别是关注伴随获得性免疫缺陷综合征(AIDS)的神经后遗症。这些努力将受益于执行，受益于调查人员的丰富经验、现有样本集、人类和非人类灵长类反应的比较以及补充数据和技术的广泛使用(例如免疫学和微阵列分析)。通过利用PNNL在蛋白质组应用的质谱学方面的经验和专业知识，蛋白质组学核心将使用高分辨率分离和质谱学来支持以下三个项目。 项目1：使用高通量蛋白质组学来确定HIV感染中与脑损伤、鞘内免疫激活、中枢神经系统感染和阿片类药物使用有关的脑脊液(CSF)蛋白质组的变化。 项目2：探索阿片类药物对非人类灵长类动物(NHP)的蛋白质组、免疫学和遗传学特征的影响，这些非人类灵长类动物(NHP)未感染或有致病性或非致病性SIV感染。 项目3：评估海洛因、丁丙诺啡和蛋白酶抑制剂对感染或未感染艾滋病毒的阿片依赖患者的免疫调节作用。