Omics analysis of HIV during synthetic opioid exposure

合成阿片类药物暴露期间 HIV 的组学分析

• 批准号: 10548205
• 负责人: JASON T BLACKARD
• 金额: $ 60.46万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10548205
• 关键词: Affect; Alcohols; Area; Bioinformatics; CD4 Positive T Lymphocytes; Cell Communication; Clinic; Cocaine; Communities; Complex; Data; Disease Progression; Epidemic; Equipment; Fentanyl; HIV; HIV Infections; HIV Long Terminal Repeat; HIV Seropositivity; HIV diagnosis; Health Services Accessibility; Heroin; In Vitro; Individual; Institution; Knowledge; Literature; Location; Long Terminal Repeats; Macrophage; Mediating; Medicine; Methadone; Methamphetamine; MicroRNAs; Midwestern United States; Morbidity - disease rate; Morphine; Ohio; Opioid; Opioid Receptor; Overdose; Pathology; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Persons; Pharmaceutical Preparations; Predisposition; Prevention program; RNA; Recreation; Research; Risk; Series; Signal Pathway; Signal Transduction; Substance abuse problem; Technology; Translational Research; Universities; Viral; Virus; addiction; adverse outcome; cell type; college; comorbidity; experimental study; fentanyl use; fundamental research; high reward; high risk; high risk sexual behavior; in vivo; injection drug use; monocyte; mortality; novel; opioid abuse; opioid epidemic; opioid exposure; opioid use; opioid use disorder; opioid user; reactivation from latency; single-cell RNA sequencing; synthetic opioid; transcription factor; transcriptome; transmission process; treatment optimization

Abstract The US is in the midst of a major opioid epidemic largely attributed to synthetic opioids. For example, fentanyl is 50-100 times more potent than heroin and is involved in >60% of overdoses nationwide and >90% of overdoses in Ohio, although this is almost certainly an underestimate of recreational use. Individuals with opioid use disorder are at significant risk for transmission of HIV, and new cases of HIV are on the rise in the Midwest and at our institution. Opioid receptors are expressed in a variety of cell types that are susceptible to HIV infection. Commonly abused opioids promote HIV replication and virus-mediated pathology. Thus, translational research on virus-opioid interactions is essential for optimized treatment and limiting viral reactivation. Important knowledge regarding how synthetic opioids influence HIV latency and reactivation is absent from the available literature. To fill this critical gap and institute a major shift forward in our understanding of this epidemic, we propose a series of complementary in vivo studies to directly evaluate the impact of synthetic opioids on markers of HIV latency/reactivation, viral diversity, transcription factor expression, microRNA expression, and cell signaling pathways.

摘要 美国正处于一场主要的阿片类药物流行之中，这在很大程度上归因于合成阿片类药物。例如, 芬太尼的效力是海洛因的50-100倍，全国60%的过量用药与芬太尼有关，90%的过量用药与芬太尼有关 俄亥俄州的过量使用，尽管这几乎可以肯定低估了娱乐用途。具有以下特征的个人 阿片类药物使用障碍有很大的艾滋病毒传播风险，新的艾滋病毒病例正在上升。 在中西部和我们的机构。阿片受体在多种易感细胞中表达。 对艾滋病病毒的感染。通常滥用的阿片类药物会促进艾滋病毒复制和病毒介导的病理。因此， 对病毒-阿片类药物相互作用的翻译研究对于优化治疗和限制病毒是必不可少的 重新激活。关于合成阿片类药物如何影响艾滋病毒潜伏期和重新激活的重要知识 没有出现在现有的文献中。为了填补这一关键空白，并在我们的 为了了解这种流行病，我们提出了一系列补充的体内研究，以直接评估 合成阿片类药物对HIV潜伏/再激活标志物、病毒多样性、转录因子的影响 表达、微RNA表达和细胞信号通路。