# Persistent HIV-1 expression and microglia dysfunction

> **NIH NIH R01** · BOSTON MEDICAL CENTER · 2021 · $759,381

## Abstract

ABSTRACT/PROJECT SUMMARY
Microglia are long-lived central nervous system (CNS)-resident innate immune cells that have critical immune
surveillance functions and homeostatic functions in the brain including clearance of pathogens and maintaining
integrity of neuronal synapses. Microglia are targeted by HIV, have been proposed to be a reservoir for HIV
persistent infection and are mediators of HIV-associated inflammation and neuropathogenesis. Importantly,
microglia dysfunction is proposed to contribute to HIV associated neurodegeneration and inflammation even
when HIV replication is suppressed during antiretroviral treatments. The mechanisms, direct or indirect, that
drive microglia to promote inflammation during HIV infection have not been elucidated. In this study, we will
utilize a primary microglia-neuron coculture model derived from pluripotent stem cells to test the hypothesis
that HIV in microglia establishes persistently infected microglia that express aberrant viral RNAs, including
those that retain intronic sequences, which mediate inflammasome activation to drive microglia dysfunction,
CNS inflammation and neuronal injury. Our preliminary data supporting our hypothesis includes results
demonstrating that primary macrophages harbor defective HIV proviruses and, despite harboring deletions and
mutations that attenuate virus production, generate HIV RNAs. Furthermore, our previous work established the
potential role of HIV intron containing RNA in activating inflammatory activities in macrophages and microglia.
Specific questions addressed in this proposal include: 1) what is the status of proviruses in HIV infected
microglia; 2) what mechanisms drive persistent expression of HIV RNA in microglia; and 3) what are the
mechanisms that trigger inflammasome activation in HIV-activated macrophages? Completion of this project
will provide general insights into the impact of HIV-1 persistence and expression in the context of
microglia. Importantly, these studies will provide insights into mechanisms that contribute to HIV-1
CNS comorbidities which persist even with ART and could lead to new targets and strategies for
treatments that will improve the lives of people living with HIV.

## Key facts

- **NIH application ID:** 10327546
- **Project number:** 1R01DA055488-01
- **Recipient organization:** BOSTON MEDICAL CENTER
- **Principal Investigator:** SURYARAM GUMMULURU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $759,381
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327546

## Citation

> US National Institutes of Health, RePORTER application 10327546, Persistent HIV-1 expression and microglia dysfunction (1R01DA055488-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10327546. Licensed CC0.

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