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由合成阿片类药物引起的阿片类药物流行之中。比如说， 芬太尼的效力是海洛因的50-100倍，在全国范围内超过60%的过量用药和超过90%的过量用药中， 在俄亥俄州的过量使用，虽然这几乎肯定是一个低估的娱乐用途。人士 阿片类药物使用障碍是艾滋病毒传播的重大风险，艾滋病毒的新病例正在增加， 中西部和我们的机构。阿片受体在多种细胞类型中表达， 艾滋病毒感染。经常滥用的阿片类药物促进艾滋病毒复制和病毒介导的病理学。因此，在本发明中， 病毒-阿片类药物相互作用的转化研究对于优化治疗和限制病毒感染至关重要。 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再激活的重要知识是 在现有文献中没有。为了填补这一关键空白，并在我们的社会中实现重大转变， 了解这种流行病，我们提出了一系列补充体内研究，以直接评估 合成阿片类药物对HIV潜伏/再激活、病毒多样性、转录因子标记物影响 表达，microRNA表达和细胞信号传导途径。