# HIV-1 Detection and Elimination From CNS Mononuclear Phagocytes

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $688,500

## Abstract

ABSTRACT
Mononuclear phagocytes (MP; monocytes, macrophages, dendritic cells. and microglia) serve as human
immunodeficiency virus type one (HIV-1) reservoirs, sites of viral persistence and latency, and inducers of end-
organ disease. All are commonly linked to HIV-1 pathobiology. However, the key relevance of the MP viral
reservoir rests in the central nervous system (CNS) of those people living with HIV (PLWH). In those PLWH and
receiving antiretroviral therapy (ART), the evidence for the size, scope, and disease relevance of the CNS viral
reservoir remains under appreciated. The discordance between laboratory MP infection and tissue persistence
in an infected human host is also not yet known. MP can have an extended life span and possess self-renewing
potential, and as such, are likely more relevant in disease than currently appreciated. Evaluation of the
significance of MPs, in general, and the microglia specifically will help define the importance of MPs during
natural infection. For the CNS specifically, HIV-1 enters the brain soon after infection and replicates in
perivascular macrophages and MGL along with limited numbers of astrocytes. Viral set point and timing of ART
initiation determines the latent reservoir size; each affects the efficiency of any eradication strategy. Knowledge
of the viral dynamics, CNS viral invasion, susceptibility to MP infection, and composition of CNS HIV reservoir
will facilitate effective therapeutic interventions. To each of these ends, we will employ novel techniques to study
the MP HIV-1 reservoir in laboratory systems and in a newly developed human microglial mouse model of human
disease. We will use basic and applied MP biology, theranostics, novel ART nanoformulations, molecular and
cellular biology, and our unique animal model to study the means to eliminate viral infection at the subcellular,
cellular, and tissue level with newly designed and novel therapeutic methods that include gene therapy
strategies. Our aims are to determine the efficiency of viral suppression by native and nanoformulated ART (at
subcellular level), assess the breadth of the CNS viral reservoirs against viral set points (defined by the initiation
of ART), and to explore combination strategies for HIV-1 elimination in a new developed humanized microglial
mouse.

## Key facts

- **NIH application ID:** 10327550
- **Project number:** 1R01NS126089-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Howard E Gendelman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $688,500
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327550

## Citation

> US National Institutes of Health, RePORTER application 10327550, HIV-1 Detection and Elimination From CNS Mononuclear Phagocytes (1R01NS126089-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10327550. Licensed CC0.

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