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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的美国正处于阿片类药物大流行之中，这主要归因于合成阿片类药物。例如，芬太尼的效力比海洛因强 50-100 倍，全国超过 60% 的吸毒过量事件与芬太尼有关，超过 90% 的吸毒过量事件与芬太尼有关俄亥俄州吸毒过量的情况，尽管这几乎肯定低估了娱乐用途。个人有阿片类药物使用障碍存在传播艾滋病毒的重大风险，并且艾滋病毒新发病例在该地区呈上升趋势中西部和我们的机构。阿片受体在多种易感细胞类型中表达到艾滋病毒感染。经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学。因此，病毒与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传播至关重要重新激活。有关合成阿片类药物如何影响 HIV 潜伏期和重新激活的重要知识现有文献中不存在。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来直接评估合成阿片类药物对 HIV 潜伏期/再激活标记、病毒多样性、转录因子的影响表达、microRNA 表达和细胞信号通路。