Distinct roles of dopamine receptors in HIV latency reversal in a myeloid cell model.

Overview

1. San Diego Biomedical Research Institute, San Diego, CA, United States
2. National Institute for Drug Abuse, Summer Internship, 2023, San Diego, CA, United States
3. Department of Psychiatry, University of California, San Diego, San Diego, CA, United States
4. Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, United States

Abstract

Background: Currently, studies on the interactions between neurotransmitters and immune cells that are targets of HIV are limited by a focus on single pathways at a time. The latent myeloid reservoir cells in the brain are a source of virus responsive to changes in the levels of dopamine (DA), caused by stimulant drugs such as methamphetamine (Meth), which, in part, explains the poor control of brain viral load in models of chronic Meth exposure. Among the effects of DA, HIV latency reversal is observed in a proportion of latent cells that turn on the transcription of viral genes. In this study, our goal was to define the specific DA receptors and pathways involved in latency reversal by DA, under the hypothesis that downstream effects of DA activating HIV transcription can be learned and serve as targets for future therapeutic purposes.

Methods: We focused on DA receptor (DRD)1 and DRD4, using the selective agonists SKF38393 hydrobromide and PD168077 maleate, which, like DA, increased levels of p24 in culture supernatants. A single-cell approach identified cells and enriched phenotypes associated with positive transcription of HIV genes.

Results: Interestingly, we found very little overlap between DA and the individual receptor clusters, pathways, and upstream regulators, while the two receptors exhibited higher phenotypic cluster similarities and a higher number of perturbed genes indicating cross-regulation. Yet, between conditions, different pathways were convergent in isolated signatures and by their overall involvement in inflammation.

Discussion: While Meth was a major contextual motivation for this work, the implications of these findings extend beyond stimulant use disorders, indicating that neuroimmune interactions are complex with resulting phenotypes derived from a combination of signaling pathways. The results suggest that latency reversal by DA in myeloid targets, especially in the brain, can occur with the contribution of DRDs’ signaling via a diversity of inflammatory pathways that have cell activation as a common feature.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE221531, at NCBI GEO; found in the text, “Data normalization, batch correction, and…”

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 8 authors, 6 keywords, 11 MeSH terms, 1 funder, 80 references.

Cite

This paper

Basova, L. V., Riley, T., Delorme-Walker, V., de Siqueira-Lima, D., Milner, R., Ellis, R. J., Fox, H., & Marcondes, M. C. G. (2026). Distinct roles of dopamine receptors in HIV latency reversal in a myeloid cell model. Frontiers in immunology, 17, 1817754. https://doi.org/10.3389/fimmu.2026.1817754

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