# HIV innate sensing in glial cells and inflammation

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2022 · $260,223

## Abstract

Project Summary
Even in the era of combination antiretroviral therapy (cART), people living with HIV (PLWH) exhibit a broad
spectrum of neurocognitive disorders collectively termed HIV-Associated Neurocognitive Disorders (HAND).
Inflammation in the brain is a hallmark of HAND, yet the mechanisms that drive this inflammation in the cART
era are not entirely clear. cART penetration into the brain is lower than in other tissues and can also lead to
production of noninfectious particles. Under these two scenarios, viral innate sensing may be triggered in glial
cells (microglia and astrocytes) to mediate persistent inflammation. We will assess mechanisms of innate
sensing in glial cells. Based on our body of work, we hypothesize that the activation of the cGAS/STING innate
sensing pathway is strong and lasting after detection of HIV particles or virus like particles in glial cells, leading
to inflammatory cytokine production which, in turn, will result in persistent neuroinflammation. Specifically, we
will determine the impact of HIV post-entry events on innate immune sensing in glial cells (aim 1) and
determine the biologic consequence of HIV-mediated innate sensing on astrocytes, either directly or through
cross-talk with microglia (aim 2). We will use iPSC-derived microglia and astrocytes in our studies as well as
sophisticated molecular, biochemical, and imaging tools to address our overall hypotheses. Our work will
define a novel pathway that may drive and/or contribute to persistent neuroinflammation in the era of cART,
which can inform targeted strategies to ameliorate and/or reduce HIV-associated neuroinflammation.

## Key facts

- **NIH application ID:** 10484086
- **Project number:** 1R21MH129205-01A1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Joao Filipe Inacio Mamede
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $260,223
- **Award type:** 1
- **Project period:** 2022-05-09 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484086

## Citation

> US National Institutes of Health, RePORTER application 10484086, HIV innate sensing in glial cells and inflammation (1R21MH129205-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10484086. Licensed CC0.

---

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