Effect of fentanyl on HIV expression in peripheral blood mononuclear cells

Janani Madhuravasal Krishnan; Krishna M Roskin; Heidi L Meeds; Jason T Blackard

doi:10.3389/fmicb.2024.1463441

Effect of fentanyl on HIV expression in peripheral blood mononuclear cells

Front Microbiol. 2024 Sep 25:15:1463441. doi: 10.3389/fmicb.2024.1463441. eCollection 2024.

Authors

Janani Madhuravasal Krishnan¹, Krishna M Roskin^{2

3}, Heidi L Meeds¹, Jason T Blackard^{1

4}

Affiliations

¹ Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
² Divisions of Biomedical Informatics and Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
⁴ Center for Addiction Research, University of Cincinnati College of Medicine, Cincinnati, OH, United States.

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 HIV_NL4-3, 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.

Keywords: CD4+ T lymphocytes; HIV; PBMC; drug use; fentanyl; opioid; single-cell RNA sequencing.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Institute on Drug Abuse grant R61/R33 DA 048439 and the National Institute on Alcohol Abuse and Alcoholism R01 AA 030486.