# Single Cell Analysis of Epigenetic Mechanisms that Regulate HIV-1 CNS Latency and Neuropathogenesis

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $716,558

## Abstract

Current antiretroviral therapies (ART) are successful in suppressing HIV-1 replication in most individuals.
However, cessation of ART results in emergence of HIV-1 from a latent viral reservoir, thereby requiring a
lifetime ART regime. The best-described HIV-1 reservoir is that of CD4+ T lymphocytes in circulating blood
and lymphoid tissues that contain a transcriptionally silent but replication-competent virus. The brain is also an
important viral reservoir site, but it is poorly characterized due to the challenges in obtaining specimens for
analyses. Despite its effectiveness, multiple toxicities are associated with ART, especially the high prevalence
of HIV-associated neurocognitive deficits. The research described in this application will use human autopsy
specimens to investigate two key issues regarding HIV-1 infection of the brain: 1) epigenetic mechanisms that
regulate active and latent HIV-1 infection in the brain; 2) mechanisms underlying neuropathogenesis and
neurocognitive deficits in HIV-1-infected individuals on suppressive ART. Brain specimens from prefrontal
cortex and hippocampus from HIV-1 infected individuals treated with ART death will be obtained from the
National NeuroAIDS Consortium. Matched HIV-1-negative control specimens will be obtained from the
UTHealth Brain Collection. Single cell RNA sequencing technology will be utilized to identify long noncoding
RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs) that are dysregulated in HIV-1-infected individuals.
Validation experiments will be performed in HIV-1-infected microglia cells to identify dysregulated lncRNAs and
miRNAs that contribute to HIV-1 replication, latency, and neuropathogenesis. Completion of the proposed
work is likely to identify therapeutic approaches to treat HIV-1 infection of the brain.

## Key facts

- **NIH application ID:** 10881965
- **Project number:** 5R01MH134392-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** CRISTIAN COARFA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $716,558
- **Award type:** 5
- **Project period:** 2023-07-06 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881965

## Citation

> US National Institutes of Health, RePORTER application 10881965, Single Cell Analysis of Epigenetic Mechanisms that Regulate HIV-1 CNS Latency and Neuropathogenesis (5R01MH134392-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10881965. Licensed CC0.

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