Krishnan Janani Madhuravasal, Roskin Krishna M, Meeds Heidi L, Blackard Jason T
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Divisions of Biomedical Informatics and Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Front Microbiol. 2024 Sep 25;15:1463441. doi: 10.3389/fmicb.2024.1463441. eCollection 2024.
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.
CD4 T lymphocytes from HIV-negative donors were activated, infected with HIV, 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 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.
The results of our findings suggest that fentanyl promotes HIV replication , emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder.
非法药物的使用,尤其是合成阿片类药物芬太尼,给全球健康带来了重大挑战。先前的研究表明,芬太尼会增强病毒复制;然而,其影响HIV发病机制的具体方式仍不清楚。本研究调查了芬太尼对CD4 T淋巴细胞中HIV复制的影响。
从HIV阴性供体中获取CD4 T淋巴细胞,进行激活、感染HIV,并给予芬太尼处理。分别使用实时PCR和ELISA对HIV前病毒DNA和p24抗原表达进行定量分析。对单细胞RNA文库进行分析以鉴定差异表达基因。
结果表明,芬太尼处理可增加HIV p24表达和前病毒DNA水平,而纳曲酮可减轻这些影响。单细胞RNA测序分析确定了CD4 T淋巴细胞中基因表达的显著变化。
我们的研究结果表明,芬太尼会促进HIV复制,强调需要更深入地了解阿片类药物与病毒的相互作用,以便为患有HIV和阿片类药物使用障碍的个体制定更好的治疗策略。