# Revealing the single cell determinants of brain relevant to persistent HIV infection and opioid use disorder

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $2,245,174

## Abstract

PROJECT SUMMARY
People living with HIV (PLWH) are at the higher risk for impaired cognitive functions such as
HIV-Associated Neurocognitive Disorder or HAND. Further, higher use of legal and illegal
opioids among PLWH could affect their immune functions and exacerbate CNS impairment.
However, little is known about the HIV harboring cell types in brain, effect of ART on specific
CNS cell types, and the modification of brain functions by opioid use. The human brain is
composed of an enormous diversity of cell types defined by distinct gene expression,
morphology, connectivity, and physiology. Single cell sequencing assays enable cell type-
specific analysis of the role of these cell types in healthy brain function and disease. The overall
objective of this proposal is to reveal the single cell determinants of brain relevant to persistent
HIV infection and opioid use disorder using snRNA-seq and snATAC-seq technologies,
bioinformatics approaches, and validation studies. Opioids, as with other addictive drugs, affect
nucleus accumbens (NAc) and prefrontal cortex (PFC) and both of these regions are also
affected by HIV. We put forward an unprecedented concept and experimental system to identify
single cell determinants of brain relevant to persistent HIV infection and opioid use disorder as
well as potential opportunities to illuminate how genetic variation affects gene expression. Our
project has two specific aims: Aim 1: Create a single nucleus transcriptomic atlas of PFC and
NAc. snRNA-seq will be performed on these two regions isolated from post mortem brains. Aim
2: Create a single nucleus epigenomic atlas of PFC and NAc. snATAC-seq will be performed on
these two regions isolated from post mortem brains. Successful completion of these innovative
single-cell studies will generate cellular part list for two NIDA-relevant brain regions, PFC and
NAc, and will illuminate novel insights into transcriptomic and epigenetic landscapes of CNS
and how they are altered by HIV and opioid use.

## Key facts

- **NIH application ID:** 10492437
- **Project number:** 5U01DA053630-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** TARIQ M RANA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,245,174
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492437

## Citation

> US National Institutes of Health, RePORTER application 10492437, Revealing the single cell determinants of brain relevant to persistent HIV infection and opioid use disorder (5U01DA053630-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10492437. Licensed CC0.

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