# Dynamic interaction between HIV in the CNS and peripheral organs

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $738,745

## Abstract

Abstract: Ample evidence from animal and human studies demonstrate that HIV infects the brain
during acute stage of the disease, setting the stage for inflammatory responses culminating in a clinical
manifestation of HIV-Associated Neurocognitive Disorders (HAND). It is unknown whether long lived-infected
brain cells release productive virus that can egress from the brain to re-seed peripheral organs. Astrocytes are
the predominate cell type in the brain and while they resist HIV fusion, they can support HIV entry though
alternative mechanisms, and HIV integration and re-activation of latent HIV. Given the inability for invasive
studies to examine the role of the CNS in general and astrocytes in particular as a reservoir for HIV in humans
and its dynamic interaction with peripheral organs, we developed a chimeric human astrocyte/human
peripheral blood mononuclear cell mouse model to address the role of astrocytes in harboring replication
competent HIV and in dissipating HIV from the brain to the periphery. We demonstrate astrocyte-initiated
replication competent HIV spread from the brain to the spleen and lymph nodes. In this application, we
propose to determine the mechanism by which HIV egress from the brain to peripheral organs (Aim 1),
evaluate HIV egress from HIV infected astrocytes to peripheral organs under combination antiretroviral therapy
(cART) (Aim 2), and assess viral evolution within the brain and between the brain and peripheral organs over
time (Aim 3). Collectively our studies will establish a paradigm shift and a greater understanding of the dynamic
interaction of HIV between the brain and peripheral organs, which can inform novel CNS-targeted therapeutic
interventions.

## Key facts

- **NIH application ID:** 10063582
- **Project number:** 5R01NS108796-03
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Lena Al-Harthi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $738,745
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063582

## Citation

> US National Institutes of Health, RePORTER application 10063582, Dynamic interaction between HIV in the CNS and peripheral organs (5R01NS108796-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10063582. Licensed CC0.

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