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: 8357610
• 负责人: RICHARD D SMITH
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357610
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Biological Assay; Cercopithecus pygerythrus; Cessation of life; Complex; 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; Lymphocyte; Macaca mulatta; Macaca nemestrina; Modeling; Morphine; National Center for Research Resources; Neurologic; Opioid; Pathogenesis; Pathologic; Primates; Principal Investigator; Proteins; Proteomics; Protocols documentation; Research; Research Infrastructure; 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; cost; 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. 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. 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).

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。 该项目正在应用强大的蛋白质组学技术来研究与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协同作用，破坏免疫功能的稳定；这被认为是艾滋病毒阳性、海洛因滥用者艾滋病毒脑炎频率和严重性增加的一个机制。阿片类药物还可能加剧猴免疫缺陷病毒(SIV)的感染，因为吗啡依赖的恒河猴在接受SIVmac239挑战时，病毒复制增加，疾病恶化，死亡加速。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？或者2)阿片类药物是否抑制了炎症反应，否则会加速疾病的发展，从而减缓疾病的速度？阿片类药物和免疫缺陷病毒之间的复杂相互作用正在由SIV诱导的慢病毒致病的明确定义的非人灵长类动物模型中进行研究，并在HIV感染和未感染的人中进行研究，无论是否使用外源性阿片类药物治疗。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特征和图谱，特别强调伴随艾滋病的神经后遗症。非人灵长类动物的样本在为期3个月的实验过程中获得，无论是否存在吗啡，以及是否存在SIVagm.sab挑战；感染SIVagm.sab的对象是尾辫猕猴和非洲绿猴，这两种猴通常分别表现出致病性和非致病性感染。我们努力探索阿片类药物对蛋白质组、免疫学和基因组图谱的影响，将受益于研究人员的丰富经验、现有的样本集、人类和非人类灵长类动物反应的比较，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)。