The HIV-associated Opioid Micro-Environment (HOME) Project

HIV 相关阿片类药物微环境 (HOME) 项目

• 批准号: 10056153
• 负责人: Sara Gianella Weibel
• 金额: $ 236.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056153
• 关键词: AIDS/HIV problem; ATAC-seq; Abdomen; Address; Adipose tissue; Alcohol or Other Drugs use; Alcohols; Anatomy; Area; Atlases; Autopsy; Basal Ganglia; Biological Assay; Blood; Brain; CD4 Positive T Lymphocytes; Categories; Cell Nucleus; Cells; Cerebrospinal Fluid; Cervix Uteri; Cessation of life; Chromatin; Chronic Disease; Clonal Expansion; Clonality; Cocaine; Collection; Colon; Communities; Cyclohexanes; DNA; DNA Integration; Data; Disease; Environment; Freezing; Funding; Gap Junctions; Genetic Transcription; Genital system; Genome; Gifts; Goals; HIV; HIV Genome; Heart; Hour; Human body; Immune; Immunologics; Individual; Inflammation; Infrastructure; Investments; Laboratories; Length; Life; Liquid substance; Liver; Lung; Lymphoid Tissue; Malignant Neoplasms; Maps; Marijuana; Mass Fragmentography; Measures; Methamphetamine; Methods; Modernization; Molecular; Morphine; Myocardial Infarction; Opioid; Outcome; Ovary; Parents; Participant; Pathway interactions; Pattern; Pericardial body location; Persons; Polymerase Chain Reaction; Population; Prostate; Proviruses; RNA; Regimen; Reporting; Research Priority; Resolution; Sampling; Site; Source; Spleen; Stroke; Substance abuse problem; T cell clonality; T-Cell Receptor; T-Lymphocyte; Techniques; Technology; Testis; Time; Tissue Sample; Tissues; Toxicology; Transcript; United States National Institutes of Health; Urine; Ursidae Family; Viral; antiretroviral therapy; base; cohort; deep sequencing; digital; frontal lobe; ileum; innovation; integration site; kidney cortex; lymph nodes; mass spectrometer; migration; multiple omics; opioid exposure; opioid use; outreach; prescription opioid; programs; reproductive tract; single-cell RNA sequencing; therapy development; transcriptome sequencing; transcriptomics; volunteer

Abstract The proposed `HOME' project is in the NIH/OAR high research priority area of eradicating HIV from persistent reservoirs and responsive to the parent RFA for highly innovative studies at the nexus of substance abuse and HIV/AIDS. Most HIV anatomical reservoirs are hard to reach but studying blood alone is not enough to fully characterize HIV reservoirs. Thus, we will leverage prior NIH investments in our unique `Last Gift Cohort'. No such cohort is available elsewhere. The cohort obtains blood (before death) and a uniquely large set of tissues (within 6 hours after death) comprehensively from persons with HIV (PWH) who die while on documented, suppressive antiretroviral therapy (ART). For our HOME project, we will collect the following 17 tissues/fluids: blood, gut (ileum and colon), lymph nodes, kidney cortex, spleen, lungs, liver, genital tract (prostate/testes or cervix/ovaries), adipose tissues (abdominal, subscapular and pericardial), heart, brain (basal ganglia, frontal cortex and cerebrospinal fluid). We will then use these samples for state-of-the-art `Single-Cell Multi-Omics' technologies to address the following Goals, which are directly responsive to the parent RFA: • Goal 1: To Deeply Characterize the HIV Reservoir (Size and Activity) in the Blood and Tissues at a Single Genome Level in Relation to Opioid Levels. • Goal 2: To Deeply Characterize the T Cell and HIV DNA Clonality in the Blood and Tissues to “Quantify the Distribution and Diversity of Clonal Expansion” in relation to opioid levels. • Goal 3: To identify HIV and Opioid-associated immunologic Mechanisms Associated with HIV Persistence and Increased HIV RNA Transcription at the Single Cell Level. By leveraging our unique source of tissues and data generated through state-of-art methods, we will for the first time deliver a map of HIV persistence, activity and clonality across the human body in relation to opioid use. We will also reveal comprehensive molecular details and define parameters of HIV persistence at single-cell resolution, which will uniquely advance HIV cure efforts.

抽象的 拟议的“HOME”项目属于 NIH/OAR 的高度研究优先领域，即根除持续存在的艾滋病毒 储存库并响应母版 RFA，在药物滥用和药物滥用之间进行高度创新的研究 艾滋病毒/艾滋病。 大多数艾滋病毒的解剖储存库很难到达，但仅研究血液不足以充分表征 因此，我们将利用 NIH 之前对我们独特的“最后的礼物队列”的投资。 该队列在其他地方获得了血液（在死亡之前）和一组独特的大量组织（在 6 小时内）。 死后）全面来自于在有记录的、抑制性的治疗期间死亡的艾滋病毒感染者 (PWH) 对于我们的 HOME 项目，我们将收集以下 17 种组织/液体：血液、肠道。 （回肠和结肠）、淋巴结、肾皮质、脾脏、肺、肝脏、生殖道（前列腺/睾丸或 子宫颈/卵巢）、脂肪组织（腹部、肩胛下和心包）、心脏、大脑（基底神经节、额叶） 然后，我们将使用这些样本进行最先进的“单细胞多组学”。 技术来实现以下目标，这些目标直接响应父 RFA： • 目标 1：一次性深入表征血液和组织中的 HIV 病毒库（大小和活性） 与阿片类药物水平相关的基因组水平。 • 目标 2：深入表征血液和组织中的 T 细胞和 HIV DNA 克隆，以“量化 克隆扩增的分布和多样性”与阿片类药物水平的关系。 • 目标 3：确定与 HIV 持续存在相关的 HIV 和阿片类药物相关免疫机制 单细胞水平的 HIV RNA 转录增加。 通过利用我们独特的组织来源和通过最先进的方法生成的数据，我们将首先 时间提供与阿片类药物使用相关的艾滋病毒在人体中的持久性、活动性和克隆性的地图。 还将揭示全面的分子细节并定义单细胞艾滋病毒持久性的参数 该决议将独特地推进艾滋病毒治疗工作。

项目成果

SARS-CoV-2 Seroconversion in an Adult Horse with Direct Contact to a COVID-19 Individual.

直接接触 COVID-19 个体的成年马发生 SARS-CoV-2 血清转化。

• 发表时间: 2022-05-14
• 作者: Pusterla, Nicola;Chaillon, Antoine;Ignacio, Caroline;Smith, Davey M;Barnum, Samantha;Lawton, Kaila O Y;Smith, Greg;Pickering, Bradley
• 通讯作者: Pickering, Bradley