# Single Cell Transciptomics of the Opioid Use Disorder and HIV Syndemic in the Human Brain

> **NIH NIH UM1** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $754,524

## Abstract

PROJECT SUMMARY
Persistent immune activation is the defining feature of HIV-1 infection in vivo and a driver of progression
to end-stage AIDS. Systemic immune activation in people living with HIV has been hypothesized to
account for higher incidence of chronic inflammatory diseases, including HIV-associated neurocognitive
disorders (HAND). While significant neurological complications associated with HIV-1 infection occur
years after seroconversion and is commonly coincident with progressive immunosuppression and high
viral loads, establishment of a virus reservoir in the CNS occurs with primary infection. Furthermore, acute
infection in the CNS is thought to initiate a cascade of pro-inflammatory events that result in inflammation-
induced neuronal injury and associated neurocognitive disorders that are evident even in the present
combination antiretroviral therapy (cART) era. Approximately 12 million people inject drugs globally, 13%
of these are people living with HIV. Opioid misuse is a route of HIV acquisition and a barrier to effective
antiretroviral therapy (ART). However, it is unclear whether opioid misuse changes the course of HIV
pathogenesis, especially on HIV-associated neurocognitive disorders. Our central hypothesis is that
opioid misuse exacerbates HIV pathogenesis in the CNS by dysregulating the glial population in the brain.
Our overall objective is to exploit cell type specific transcriptomic information at the single nuclei level from
patient brain samples to characterize the effects of opioid use disorder on CNS neuronal and glial cells,
HIV infection and HANDs. We will characterize single nuclei gene expression and identify dysregulated
gene regulatory networks in each of the neuronal and glial populations associated with opioid misuse in
HIV infected individuals and/or with HANDs. We will also perform computational analysis to identify
neuronal and glial cell regulatory networks altered by opioid misuse. In the validation component, we will
select the top 20 targets from single cell transcriptomics profiles, first validating with
immunohistochemistry with fixed brain tissue, then selecting a few top targets and using 2D and 3D
cultures of iPS derived neurons, microglia and astrocytes to characterize functionality with CRISPR
knockout. Successful completion of these aims will have significant research and clinical impact by 1)
elucidating how opioid misuse alters HIV/HAND pathogenesis in the CNS, and 2) discovering candidate
molecules to regulate HIV infection or persistence in the CNS in the context of opioid misuse.

## Key facts

- **NIH application ID:** 10690784
- **Project number:** 5UM1DA051411-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Christine Cheng
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $754,524
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690784

## Citation

> US National Institutes of Health, RePORTER application 10690784, Single Cell Transciptomics of the Opioid Use Disorder and HIV Syndemic in the Human Brain (5UM1DA051411-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10690784. Licensed CC0.

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