# Macrophages and Microglia, Gene Expression and Chromatin: Illuminating the Myeloid Viral Reservoir in the Brain through Single Cell Analyses

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $229,500

## Abstract

Project Summary
An innovative approach is proposed to determine the Role of Myeloid Cells in Persistence and Eradication of
HIV-1 Reservoirs from the Brain, in response to RFA-MH-20-702. We will perform using the gold-standard
nonhuman primate system, in SIV-infected animals with chronic viral suppression using combination
antiretroviral therapy. The infected cells in the brain will be uncovered by intra-CNS anti-CD8 treatment, following
subsequently by myeloid cell isolation and purification, single-cell RNA sequencing (scRNA-seq) and single-cell
Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq), followed by bioinformatic analysis and
validation. This will give result into unparalleled insight into the nature of the myeloid cells in which SIV, as a
model for HIV, persists in the brain, combining individual cellular transcriptomes with epigenetic information on
the whole genome. These will be done in a new paired format, obtaining linked information on the two modalities
from the same cell. combined with sensitive assays for virus in the brain. This will take place in the context of a
two-year R21 under two Specific Aims. In Aim 1, we will uncover the SIV-infected cells in the brain in the presence
of suppressive cART, allowing their identification and, in comparison with the information on the companion
uninfected cells, as well as known data on brain myeloid cells from single cell and other studies, the phenotype
of brain myeloid cells in which SIV/HIV can persist. In Aim 2, in-depth molecular characterization of these cells
will be performed, yielding additional information on their phenotype, as well as upstream control mechanisms,
transcriptional potential, as well as relationships to genes and their control regions that affect HIV, CNS disease,
and other conditions. We will ensure our data adhere to the Findable, Accessible, Interoperable, and Reusable
(FAIR) standards in order that we and others can utilize this information in future strategies to silence or clear
virus from the brain. These studies are designed with rigor and reproducibility factored in, thus the results from
these studies will provide new insights into the role of myeloid cells in persistence and eradication of HIV-1
reservoirs from the brain.

## Key facts

- **NIH application ID:** 10327555
- **Project number:** 1R21MH128057-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** HOWARD S FOX
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $229,500
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327555

## Citation

> US National Institutes of Health, RePORTER application 10327555, Macrophages and Microglia, Gene Expression and Chromatin: Illuminating the Myeloid Viral Reservoir in the Brain through Single Cell Analyses (1R21MH128057-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10327555. Licensed CC0.

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