# Single cell brain transcriptome changes during chronic HIV infection and opiate use in conventional mice

> **NIH NIH U01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $2,654,681

## Abstract

PROJECT SUMMARY
This application is submitted in response to RFA-D-21-019: Single Cell Opioid Responses in the
Context of HIV (SCORCH) Program Expansion: CNS Data Generation for Chronic Opioid,
Methamphetamine, and/or Cocaine Exposures. Human immunodeficiency virus (HIV) can infect
nonneuronal cells in the brain, particularly microglia, with these cells acting as a reservoir of
latent infection. HIV infection has deletions effects on the function of nonneuronal and neuronal
cells, including those cells located in brain sites relevant to cognition, emotion and motivation.
The same brain sites impacted by HIV are known to regulate the actions of opioids and other
classes of addictive drugs, and opioid use disorder (OUD) is more prevalent in HIV-infected
individuals than the general population. Moreover, HIV infection and OUD reciprocally interact,
with each condition potentially exacerbating the severity of the other. Mice infected with EcoHIV,
a modified HIV strain that targets CD4+ T cells, macrophages and microglia, recapitulates the
major pathobiological features of chronic HIV infection in individuals on antiretroviral therapy
(ART). Here, we will leverage state-of-the-art single cell sequencing (scSeq), molecular, cellular
and behavioral approaches to define cell type-specific interactions between HIV and opioids in
the brains of EcoHIV-infected mice. In Specific Aim I, we optimize the intravenous (IV) heroin
self-administration procedure, already well-established in our laboratories, for use in EcoHIV-
infected mice. We will then examine the effects of EcoHIV infection on the expression of opioid
addiction-relevant behaviors. Conversely, we will examine the effects of heroin consumption on
the expression of cognitive abnormalities in EcoHIV-infected mice relevant to HIV-associated
neurocognitive impairment (HIV-NCI) in humans. Finally, will examine the effects of ART on the
expression of addiction- and HIV-NCI-relevant behavioral abnormalities in EcoHIV-infected
mice. In Specific Aim II, we will perform scSeq on brain regions relevant to opioid addiction and
HIV-NCI, collected from EcoHIV mice with our without a history of intravenous opioid self-
administration behavior. We will investigate the effects of ART on scSeq patterns in these mice.
The scSeq data will be mined to identify cells in the brain infected by EcoHIV, and determine
which cells show the most robust transcriptional responses to EcoHIV in opioid-naïve and
opioid-experienced mice. In situ hybridization and immunohistochemistry will be used to validate
key findings and prioritize candidate genes for further investigation. In Specific Aim III, we will
use in vivo CRISPR-Cas9 to target prioritized genes identified in Aim II in a cell type- and brain
region-specific manner. The impact of CRISPR cleavage of prioritized genes on the expression
of addiction- and HIV-NCI-relevant behavioral abnormalities in EcoHIV-infected mice will be
examined. This innovative program of research ma...

## Key facts

- **NIH application ID:** 10220584
- **Project number:** 1U01DA053629-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Paul J. Kenny
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,654,681
- **Award type:** 1
- **Project period:** 2021-05-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220584

## Citation

> US National Institutes of Health, RePORTER application 10220584, Single cell brain transcriptome changes during chronic HIV infection and opiate use in conventional mice (1U01DA053629-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10220584. Licensed CC0.

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