# Investigating intercellular interactions between astrocytes and microglia in HIV infection and latency

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $34,191

## Abstract

HIV currently infects over 38 million people worldwide. Despite the high efficacy of antiretroviral
therapies, HIV persists via transcriptionally silent latent infection and long-lived viral reservoirs in
tissue sites such as the central nervous system. Viral persistence in the central nervous system
leads to sustained neuroinflammation, which in turn causes neuronal injury. As a result, a
spectrum of deficits in memory, learning, and/or motor functions referred to as HIV-associated
neurocognitive disorders can be observed in 40- 50% of people living with HIV. The largest
population of central nervous system resident cells that are susceptible to HIV infection is
microglia, the resident macrophages of the brain. Astrocytes are also impacted by HIV infection
both through abortive integration of the viral genome and through indirect activation by proinflammatory
cytokines produced by infected cells. Because microglia are challenging to model
in vitro and rarely obtainable from HIV patients, the dynamics of HIV infection in microglia as
well as the immune response of both microglia and astrocytes to HIV infection remain poorly
understood. This proposal seeks to deepen our understanding of the neuroinflammatory
response to HIV infection using IPSC models of human microglia (iMg) and astrocytes
(iAst). Recent studies have shown that peripheral macrophages respond to HIV infection by
producing IL-1β and my preliminary data suggests that HIV infected iMg also secrete IL-1β.
Additionally, coculture of iAst and iMg leads to increased HIV replication, suggesting that iAst
act to augment HIV infection. I hypothesize that IL-1β produced by infected iMg induces
TNFa production by iAst, which acts on iMg to increase productive HIV infection and
decrease latent infection. I will test this hypothesis in two aims: (1) Define the impact of
intercellular interactions between astrocytes and microglia on HIV-induced inflammation and
HIV infection, and (2) define the influence of astrocytes on HIV latency in microglia using single
cell transcriptomics. These studies will increase our understanding of HIV infection in the CNS
and the intercellular interactions that cause neuroinflammation in HIV associated neurocognitive
disorders.

## Key facts

- **NIH application ID:** 10547986
- **Project number:** 1F31MH131486-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** James Gesualdi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,191
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10547986

## Citation

> US National Institutes of Health, RePORTER application 10547986, Investigating intercellular interactions between astrocytes and microglia in HIV infection and latency (1F31MH131486-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10547986. Licensed CC0.

---

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