Janani Madhuravasal Krishnan, Krishna M Roskin, Heidi L Meeds, Jason T Blackard
{"title":"Effect of fentanyl on HIV expression in peripheral blood mononuclear cells.","authors":"Janani Madhuravasal Krishnan, Krishna M Roskin, Heidi L Meeds, Jason T Blackard","doi":"10.3389/fmicb.2024.1463441","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Illicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4<sup>+</sup> T lymphocytes.</p><p><strong>Methods: </strong>CD4<sup>+</sup> T lymphocytes from HIV-negative donors were activated, infected with HIV<sub>NL4-3</sub>, and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes.</p><p><strong>Results: </strong>Results indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4<sup>+</sup> T lymphocytes.</p><p><strong>Discussion: </strong>The results of our findings suggest that fentanyl promotes HIV replication <i>ex vivo</i>, emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461324/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmicb.2024.1463441","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Illicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4+ T lymphocytes.
Methods: CD4+ T lymphocytes from HIV-negative donors were activated, infected with HIVNL4-3, and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes.
Results: Results indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4+ T lymphocytes.
Discussion: The results of our findings suggest that fentanyl promotes HIV replication ex vivo, emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder.
导言:非法使用毒品,尤其是合成阿片类药物芬太尼,对全球健康构成了重大挑战。以前的研究表明,芬太尼能增强病毒复制;然而,芬太尼影响艾滋病发病机制的机制仍不清楚。本研究调查了芬太尼对 CD4+ T 淋巴细胞中 HIV 复制的影响:方法:激活 HIV 阴性供体的 CD4+ T 淋巴细胞,用 HIVNL4-3 感染,并用芬太尼处理。分别使用实时 PCR 和酶联免疫吸附法对 HIV proviral DNA 和 p24 抗原表达进行量化。对单细胞 RNA 文库进行分析,以确定差异表达基因:结果表明,芬太尼治疗会增加 HIV p24 的表达和病毒 DNA 的水平,而纳曲酮可以减轻这些影响。单细胞 RNAseq 分析发现 CD4+ T 淋巴细胞中的基因表达发生了显著变化:讨论:我们的研究结果表明,芬太尼会促进体内艾滋病病毒的复制,这强调了深入了解阿片类药物与病毒之间相互作用的必要性,从而为艾滋病病毒感染者和阿片类药物使用障碍患者制定更好的治疗策略。
期刊介绍:
Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.