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).

这个子项目是许多研究子项目中的一个 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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目正在应用强大的蛋白质组学技术来研究与伴随的慢病毒感染和药物滥用相关的病理事件所导致的变化。阿片类药物和HIV蛋白协同作用，通过影响单核细胞和淋巴细胞破坏免疫功能;这被认为是HIV阳性、海洛因滥用个体中HIV脑炎发生频率和严重程度增加的一种机制。阿片类药物也可能加剧猿猴免疫缺陷病毒（SIV）感染，因为吗啡依赖性恒河猴在用SIVmac 239攻击时表现出病毒复制增加、疾病加重和死亡加速。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，否则会加速疾病进展，并在这样做的过程中减缓疾病的速度？阿片类药物和免疫缺陷病毒之间的复杂相互作用正在研究一个定义明确的非人灵长类动物模型的慢病毒的发病机制诱导的SIV和HIV感染和未感染的人类受试者，治疗或不与外源性阿片类药物。我们的目标是确定定量蛋白质组生物特征和轮廓，定义和预测阿片类药物对慢病毒疾病进展的影响，特别强调伴随艾滋病的神经系统后遗症。在存在或不存在吗啡以及存在或不存在SIVagm.sab攻毒的情况下，在3个月的方案过程中获得了非人灵长类动物的标本;在猪尾猕猴和非洲绿色猴中进行了SIVagm.sab感染，这两种猴通常分别表现出致病性和非致病性感染。我们探索阿片类药物对蛋白质组学、免疫学和基因组学特征的影响的努力将受益于研究者的广泛经验、现有样本集、人类和非人类灵长类动物反应的比较以及补充数据和技术的广泛使用（例如，免疫学和微阵列测定）。