HIV PROJECT

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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，广泛研究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理学干预措施引起的蛋白质丰度变化。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，接受或不接受外源性阿片类药物治疗，以及在明确定义的猴免疫缺陷病毒（SIV）诱导的慢病毒发病机制的非人灵长类动物模型中进行研究。在这样做的过程中，我们的目标是确定定量蛋白质组生物特征和配置文件，定义和预测阿片类药物对慢病毒疾病进展的影响，特别强调伴随获得性免疫缺陷综合征（艾滋病）的神经系统后遗症。 这些努力将受益于执行的方式，受益于广泛的经验，研究人员，现有的样本集，比较人类和非人类灵长类动物的反应，并广泛使用的补充数据和技术（如免疫和微阵列检测）。通过利用PNNL在蛋白质组学应用质谱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来支持以下三个项目。 项目一：使用高通量蛋白质组学来确定与脑损伤、鞘内免疫激活、CNS感染和阿片类药物使用相关的HIV感染中脑脊液（CSF）蛋白质组的变化。 项目二：探讨阿片类药物对未感染或感染致病性或非致病性SIV的非人灵长类动物（NHP）的蛋白质组学、免疫学和遗传特征的影响。 项目三：评价海洛因、丁丙诺啡和蛋白酶抑制剂对感染或未感染HIV的阿片类药物依赖者的免疫调节作用。

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.