HIV PROTEOMIC CENTER FOR HOST-VIRAL RESPONSE CHARACTERIZATION

HIV 宿主病毒反应表征蛋白质组学中心

• 批准号: 8172780
• 负责人: RICHARD D SMITH
• 金额: $ 46.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172780
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Biological Assay; Cercopithecus pygerythrus; Cessation of life; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Disease Progression; Event; Exhibits; Fostering; Frequencies; Funding; Genomics; Grant; HIV; HIV Seropositivity; HIV encephalitis; Heroin Abuse; Human; Immune response; Immunologic Deficiency Syndromes; Immunologics; Individual; Infection; Inflammatory Response; Institution; Lymphocyte; Macaca; Macaca mulatta; Modeling; Morphine; Neurologic; Opioid; Pathogenesis; Pathologic; Proteins; Proteomics; Protocols documentation; Research; Research Personnel; Resources; SIV; Sampling; Severities; Source; Specimen; Substance abuse problem; Techniques; Technology; United States National Institutes of Health; Viral; Virus; Virus Diseases; Virus Replication; biosignature; experience; human subject; immune function; monocyte; nonhuman primate; response

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. This project is applying powerful proteomics technologies to investigate changes resulting from the pathologic events associated with concomitant lentiviral infection and substance abuse. Opioids and HIV proteins act synergistically to destabilize immune function by affecting monocytes and lymphocytes; this has been proposed as a mechanism underlying the increased frequency and severity of HIV encephalitis among HIV-positive, heroin-abusing individuals. Opioids may also exacerbate simian immunodeficiency virus (SIV) infections, as morphine-dependent rhesus macaques exhibit increased virus replication, exacerbated disease, and accelerated death when challenged with SIVmac239. The central research questions we wish to address are: 1) do opioids suppress protective immune responses and foster disease progression? Or 2) do opioids suppress inflammatory responses that would otherwise accelerate disease progression and, in so doing, slow the pace of disease? The complex interactions between opioids and immunodeficiency viruses are being studied in a well-defined nonhuman primate model of lentiviral pathogenesis induced by SIV and in HIV-infected and uninfected human subjects, treated or not with exogenous opioids. 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 AIDS. Specimens from nonhuman primates have been obtained over the course of a 3-month protocol, both in the presence or absence of morphine, as well as in the presence or absence of SIVagm.sab challenge; infection with SIVagm.sab was done in pigtailed macaques and African green monkeys, which normally exhibit pathogenic and non-pathogenic infections, respectively. Our efforts to explore the effect of opioids on proteomic, immunologic, and genomic profiles will benefit from the extensive experience of the investigators, existing sample sets, comparison of human and nonhuman primate responses, and the extensive use of complementary data and techniques (e.g., immunologic and microarray assays).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目正在应用强大的蛋白质组学技术来研究与伴随慢病毒感染和药物滥用相关的病理事件引起的变化。阿片类药物和艾滋病毒蛋白通过影响单核细胞和淋巴细胞来协同起作用，以不稳定免疫功能。这已被认为是艾滋病毒阳性，虐待海洛因的个体中HIV脑炎的频率和严重程度增加的基础机制。阿片类药物还可能加剧邻苯二甲酸免疫缺陷病毒（SIV）感染，因为当对SIVMAC239挑战时，依赖吗啡依赖性恒河猕猴在病毒复制，加重疾病和加速死亡时会增加。我们希望解决的中心研究问题是：1）阿片类药物是否抑制保护性免疫反应并促进疾病进展？或2）阿片类药物会抑制炎症反应，否则会加速疾病的进展，并且这样做会减慢疾病的速度？阿片类药物与免疫缺陷病毒之间的复杂相互作用正在由SIV和HIV感染和未感染的人类受试者诱导的慢病毒发病机理的明确定义的非人类灵长类动物模型中进行了研究，并接受了外源性阿片类药物的治疗。我们旨在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学生物签名和特征，并特别强调了伴随辅助的神经系统后遗症。在存在或不存在吗啡的情况下，以及在存在或不存在Sivagm.Sab挑战的情况下，已获得了非人类灵长类动物的标本。 Sivagm.Sab的感染是在锯齿状猕猴和非洲绿猴中进行的，这些猴子通常表现出致病性和非致病感染。我们为探索阿片类药物对蛋白质组学，免疫学和基因组概况的影响的努力将受益于研究人员的广泛经验，现有样本集，人类和非人类灵长类动物反应的比较以及广泛使用补充数据和技术（例如，免疫学和微rar虫分析）。