# Single-cell multi-omic analysis of opioid-mediated HIV disease pathogenesis

> **NIH NIH R61** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $497,860

## Abstract

Abstract
Routine HIV treatment with combination antiretroviral therapy (cART) eliminates nearly all actively infected cells.
Nevertheless, the small reservoir of residual cells, some of which can remain dormant for long periods of time
before becoming active and producing new virus particles, represents a crucial barrier to completely curing the
disease. Substance use disorders introduce further challenges—for example, many immune cells express opioid
receptors and undergo significant molecular changes after opioid exposure, which can increase their vulnerability
to HIV infection. Our recent work suggests that the global transcriptomic and epigenomic changes during
hematopoietic differentiation affect viral latency and activation. Additionally, we recently found that global
inhibition of histone deacetylase activity in HSPCs increases viral activation, further implicating epigenomic
changes in activation. Deciphering the contributions of addictive substances, inflammatory stimuli, and cell state
to HIV infection and latency is crucial for ongoing efforts to cure HIV. In particular, the following fundamental
questions remain unanswered: How does substance use change the transcriptomic and epigenomic states of
immune cells? How do these changes in turn affect HIV infection and latency? How do the effects of substance
use on HIV infection and latency vary across different immune cell types and states? Here, we will combine our
experimental platform for identifying latently and actively infected cells, single-cell transcriptome, and epigenome
sequencing, and our recently developed computational integration methods to investigate these questions. Our
interdisciplinary team combines expertise in HIV basic science, HIV clinical treatment, and bioinformatics to
develop an experimental and computational framework for integrated gene expression, chromatin accessibility,
histone modification, and insertion site profiling into a single picture of how opioids affect viral infection and
latency. Specifically, this project will (1) use single-cell RNA-seq, single-cell ATAC-seq, and single-cell Cut&Tag
to map diversity of infected cell response to opioid exposure, (2) investigate the relationship between immune
cell type and differentiation state and viral activation, and (3) determine viral integration sites through single-cell
RNA-seq. Together, these aims will produce a comprehensive, integrated transcriptomic and epigenomic atlas
of how HIV-infected immune cells respond to opioid exposure as well as how opioids impact HIV infection. Our
work also develops a broadly applicable experimental and computational framework, laying a foundation for the
discovery of novel insights into HIV infection and latency in the context of substance use disorders.

## Key facts

- **NIH application ID:** 10932341
- **Project number:** 5R61DA059916-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kathleen L. Collins
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,860
- **Award type:** 5
- **Project period:** 2023-09-30 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932341

## Citation

> US National Institutes of Health, RePORTER application 10932341, Single-cell multi-omic analysis of opioid-mediated HIV disease pathogenesis (5R61DA059916-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10932341. Licensed CC0.

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