# Effects of CSF1R Blockade on Repopulation of SIV Reservoirs from the CNS to the Periphery After Antiretroviral Therapy Interruption

> **NIH NIH R01** · BOSTON COLLEGE · 2024 · $697,085

## Abstract

Abstract
Despite effective anti-retroviral therapy (ART) that maintains HIV at non-detectable levels in plasma, HIV is not
eradicated. When individuals are off ART, or during viral blips, CNS viral reservoirs can quickly rebound. We
and others have found that a population of CNS perivascular macrophages (PVMs) function as a major target
for HIV and SIV infection in the CNS, and the viral reservoir that persists with ART. Intracisternal (i.c.) injection
of superparamagnetic iron oxide nanoparticles (SPIONs) demonstrate PVMs take up SPIONs within the CNS,
accumulate with SIV infection, and traffic out of the CNS where they are found in cervical draining lymph nodes
(cLNs), dorsal root ganglia, spleen, and bone marrow. Importantly, SPION-labeled CD163+ macrophages in the
cLN can be productively infected with SIV as evidenced by SIV-p27 immunoreactivity. It is our overall
hypothesis that an identifiable population of PVMs in the CNS functions as a cellular reservoir of rebound HIV
and SIV during ART, and after ART cessation, and these cells can leave the CNS with virus that potentially
reseeds the periphery. To test our hypothesis, we propose to use a CNS-penetrant colony-stimulating factor 1
receptor (CSF1R) inhibitor (BLZ945) that ablates these reservoir-reseeding CNS PVM early (3 months after ART
initiation) and late (5 months after ART initiation) during ART in virally suppressed macaques, and in animals
undergoing ART cessation. We propose to use 2 different fluorescently tagged SPIONs, injected intra-CSF just
prior to early and late BLZ945 treatments, in order to define the role of resident and repopulated PVMs to function
as a viral reservoir of SIV, and block their ability emigrate with virus. We propose to test our hypothesis with two
Specific Aims: Aim 1 will determine the extent to which CSF1R blockade can eradicate SIV in the brain and block
lymphatic-dependent reseeding of virus from the CNS to the periphery in the presence of ART; and Aim 2 will
determine whether CSF1R blockade can prevent reactivation of SIV reservoirs in the brain and repopulation of
viral reservoirs from the CNS to the periphery after ART interruption.

## Key facts

- **NIH application ID:** 10872289
- **Project number:** 5R01NS126091-04
- **Recipient organization:** BOSTON COLLEGE
- **Principal Investigator:** Woong-Ki Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $697,085
- **Award type:** 5
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872289

## Citation

> US National Institutes of Health, RePORTER application 10872289, Effects of CSF1R Blockade on Repopulation of SIV Reservoirs from the CNS to the Periphery After Antiretroviral Therapy Interruption (5R01NS126091-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10872289. Licensed CC0.

---

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