# Targeting of SIV Macrophage Reservoirs in the CNS by CSF1R Inhibition

> **NIH NIH R01** · EASTERN VIRGINIA MEDICAL SCHOOL · 2020 · $687,822

## Abstract

Project Summary
Despite the advent of highly active antiretroviral therapy (HAART), HIV-associated neurocognitive disorders
remain surprisingly common. HIV and the closely-related simian immunodeficiency virus (SIV) may persist in
the brain ‘sanctuary’, where access of otherwise potent antiretrovirals is limited. It is now becoming clear that
myeloid cells support HIV/SIV infection independently of CD4 T cells and can be the source of rebound virus in
tissues including brain upon cessation of suppressive antiretroviral therapy (ART). To date, however,
therapeutic strategies for targeting HIV in the myeloid cells and in the central nervous system (CNS) have not
yet been developed. The overall goal of this proposal is to lead collaborations to exploit the known
pharmacological colony-stimulating factor 1 receptor (CSF1R) inhibition for macrophage targeting to target
long-lived infected CSF1Rhigh myeloid cells in the CNS. Recently, we found, for the first time, overexpression
and activation of the CSF1R in CNS myeloid cells including perivascular macrophages (PVM) and activated
microglia in SIV-infected macaques with encephalitis, as well as in the brain of virally suppressed HIV patients.
We also found that CSF1R blockade in vitro selectively ablated rhesus monocyte-derived CSF1Rhigh
macrophages. Our central hypothesis is that resident CSF1Rhigh myeloid cells in the brain contribute to
persistent HIV brain infection and neuroinflammation despite HAART. Consequently, selective targeting of
infected myeloid cells by CSF1R signaling blockade will eliminate the persistent viral reservoir from the CNS.
The first aim will determine whether ablation of CSF1Rhigh myeloid cells in the CNS in during acute infection will
decrease DNA proviral load in the brain. The second aim will focus on ablating the CSF1Rhigh brain myeloid
cells in the setting of ART-treated chronic infection. The research proposed in this application is innovative
because it represents an entirely novel departure from the current approach to maintaining viral suppression in
HIV-infected patients. Our contribution here will be significant because it is a first step toward the development
of therapeutic strategies for targeting virus-infected CNS myeloid cells or inhibiting viral infection of myeloid
cells in the CNS. Once such strategies become available, there is promise that persistent myeloid HIV
reservoirs could be eradicated from brain and other tissues.

## Key facts

- **NIH application ID:** 9993548
- **Project number:** 5R01MH118139-02
- **Recipient organization:** EASTERN VIRGINIA MEDICAL SCHOOL
- **Principal Investigator:** Woong-Ki Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $687,822
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993548

## Citation

> US National Institutes of Health, RePORTER application 9993548, Targeting of SIV Macrophage Reservoirs in the CNS by CSF1R Inhibition (5R01MH118139-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993548. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*