# Development of Induced-Microglia to Investigate HAND and HIV-1 Latency

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2020 · $240,000

## Abstract

Infection of the central nervous system (CNS) results in HIV-associated neurological disorders (HAND) in up to
50% of ART-treated individuals. Infection of microglia in the CNS is involved in the etiology of HAND, as
microglia express both CD4 and CCR5 on their surface and are infected by HIV-1 in vivo. In addition to
involvement in HAND, HIV-1 infection of microglia generates a reservoir of replication-competent virus that
persists in ART-treated individuals. Knowledge about mechanisms underlying HAND and HIV-1 latency in
microglia is limited, due in considerable part to the absence of tractable and robust model systems that can
investigate HIV-1 infection of this important cell type. However, it has recently become possible to generate
induced microglia (iMicroglia) from induced pluripotent stem cell lines. Importantly, iMicroglia possess
functional properties similar to microglia in vivo, including their RNA expression profile, secretion of cytokines
in response to inflammatory stimuli, and phagocytosis of CNS substrate. The research proposed in this
exploratory R21 will develop a new model system– iMicroglia – to investigate mechanisms underlying HAND
and latent infection of the CNS. The research involves two Specific Aims. Aim 1 will use high-field NMR and
single cell RNAseq (ssRNAseq) to identify metabolic and genetic pathways that are perturbed by HIV-1
infection. Aim 2 will utilize a dual-fluorescence HIV-1 reporter virus and cell sorting to obtain infected iMicroglia
that harbor latent integrated viruses or are permissive for viral replication. SsRNAseq will identify differentially
expressed genes that are associated with viral replication or latency; latency reversal agents will be evaluated
and compared to their activities in CD4+ T cells. Completion of the proposed research may serve as the
foundation for novel therapeutic approaches, as it will provide mechanistic insight into HAND and HIV-1
latency.

## Key facts

- **NIH application ID:** 9991924
- **Project number:** 5R21MH121647-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Andrew P Rice
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991924

## Citation

> US National Institutes of Health, RePORTER application 9991924, Development of Induced-Microglia to Investigate HAND and HIV-1 Latency (5R21MH121647-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9991924. Licensed CC0.

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