# Neuroimmune axis in HAND and HIV persistence in the brain

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $551,326

## Abstract

Abstract: HIV causes a spectrum of neurologic deficits known as HIV-Associated Neurologic
Disorders (HAND). HAND is a prominent co-morbid condition of HIV even in the era of
Combined Anti-Retroviral Therapy and is expected to increase as the HIV+ population ages.
Fundamental understanding of how HIV invades the brain and mechanisms that drive HAND
are poorly understood. In this application we will focus on the role of CD4+ T cells and
CD4dimCD8bright T cells in HIV neuroinvasion, persistence, and HAND. CD4dimCD8bright T cells
are a unique subset of CD8+ T cells that co-express CD4 on their surface. They exhibit potent
anti-viral responses in the periphery. Recently, we showed that migration of CD8+ T cells into
the CNS in context of HIV gives rise to CD4dimCD8bright T cells, in a Wnt/-catenin signaling -
dependent manner. Within the brain, CD4dimCD8bright T cells exhibit highly potent anti-HIV
responses. The consequence of this response is controlling HIV on one hand but perhaps at the
cost of inducing inflammation and injury in the brain. Based on our published and preliminary
data, we hypothesize that because peripheral CD4dimCD8bright T cells are susceptible to HIV
infection, they will contribute to HIV neuroinvasion (Aim 1), yet because they robustly express
-catenin and its pro-survival target gene, Bcl-XL, infected CD4dimCD8bright T cells will persist in
the CNS as a reservoir for HIV (Aim 2). Further, because CD4dimCD8bright mount potent anti-HIV
responses and are hyper-activated, their frequency will correlate with lower HIV content in CNS
but higher level of neuroinflamamtion and worse neurocognitive performance (Aim 3). We will
use a combination of in vitro, small animal studies, and patient samples from the Southeast Asia
Research Collaboration with the University of Hawaii (SEARCH) and the US Military HIV
Research Program (USMHRP) to address this central hypothesis. Collectively our studies will
establish a new understanding of HIV neuroinvasion, HIV neuro-persistence, and role of T cells
in the neuro-immune axis mediating neuropathogenesis/HAND. This understanding can provide
new approaches for therapeutic intervention to ameliorate and/or reduce HAND and will provide
valuable insights into HIV persistence in the CNS.

## Key facts

- **NIH application ID:** 10088477
- **Project number:** 5R01MH113425-05
- **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:** $551,326
- **Award type:** 5
- **Project period:** 2017-04-20 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088477

## Citation

> US National Institutes of Health, RePORTER application 10088477, Neuroimmune axis in HAND and HIV persistence in the brain (5R01MH113425-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10088477. Licensed CC0.

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