HIV PROJECT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.