# Characterize replication competent myeloid reservoirs in the central nervous system

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $194,895

## Abstract

SUMMARY
 The eradication of HIV-1(HIV) infection must address all tissues where infection persists. Clearance of
infection in the central nervous system (CNS) is not achieved by antiretroviral therapy (ART) alone, just as in
the periphery. Latent HIV reservoirs in the CNS may allow viral rebound upon discontinuation of ART, as HIV
can egress from the brain into the peripheral blood. However, studies are needed to elucidate the contributions
of subsets of latently infected CNS cells to ongoing HIV persistence in the CNS. Circulating T cells have been
well characterized as the major HIV reservoirs in the peripheral blood, and may circulate into the CNS,
contributing to HIV persistence in the brain. Nevertheless, it is still not known whether T cells are the only
major viral reservoir in the CNS.
 Myeloid cells are a major cellular compartment of the immune system infected by HIV in the brain. In
vivo imaging and immunostaining studies have revealed that brain myeloid cells (BMCs) harbor HIV DNA and
produce HIV RNA and proteins. However, it is not clear whether BMCs, and especially long-lived microglia, are
latently infected, and if they are true HIV reservoirs encoding replication-competent HIV despite durable,
successful ART. Our team at the UNC HIV Cure Center has recently established a protocol to isolate highly
pure myeloid cells from the brain of SIV-infected macaques, in whom ART was interrupted. These SIV
containing BMCs can be cultured for many generations ex vivo. Further application of this technology to other
fully ART-suppressed animals found that BMCs contain proviral SIV DNA, and that SIV RNA can be effectively
induced by latency reversal agents. This platform to study myeloid cells ex vivo allows rigorous
characterization of brain myeloid cells to address their role as true HIV reservoirs that can produce replication-
competent viruses. Our preliminary data highlights that epigenetic regulation, such as histone deacetylation
and histone methylation, may play an essential role in the modulation of HIV latency in the CNS. We
hypothesize that BMCs are latently infected by HIV and harbor replication competent HIV.
 In this proposal, we will isolate highly pure brain myeloid cells from different regions of the brain in both
people living with HIV (PLWH) enrolled in the “Last Gift” cohort and fully ART-suppressed SIV-infected rhesus
macaques. We will examine whether BMCs harbor replication-competent HIV or SIV using the intact proviral
DNA assay (IPDA) and quantitative viral outgrowth assay (QVOA) (Aim1). We will examine whether latent HIV
in myeloid cells responds to the currently available latency reversal agents related to epigenetic regulation of
HIV latency (Aim 2), which may provide clues to the mechanisms that allow HIV latency in the brain. Our study
will address critical gaps in knowledge to better understand whether BMCs serve as true HIV reservoirs and
how HIV persists in these CNS cells.

## Key facts

- **NIH application ID:** 10432131
- **Project number:** 5R21MH128034-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Guochun Jiang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,895
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432131

## Citation

> US National Institutes of Health, RePORTER application 10432131, Characterize replication competent myeloid reservoirs in the central nervous system (5R21MH128034-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10432131. Licensed CC0.

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