# Exploring the Molecular, Neuro-immune and Behavioral changes during HIV-associated progressive aging using a long-term humanized mice model

> **NIH NIH R56** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $383,750

## Abstract

Abstract
Aging is associated with persistent levels of inflammation, which is also a hallmark of HIV infection. The effects
of aging are particularly important to the population of people living with HIV (PLWH), as the overall cohort of
infected individuals is getting older, with over 4 million over the age of 50. The reported effects of aging seen in
HIV patients are increased co-morbidities, frailty, diabetes, cardiovascular disease, increased immune
inflammation, and increased senescence, which led researchers to believe that HIV infection leads to a form of
early aging. Though, the widespread use of antiretroviral therapy (ART) allowed the disease to be medically
manageable, however, strict lifelong adherence to daily drug regimens is required. Though daily combinatorial
ART intake keeps HIV-1 at bay in tissue reservoirs, replication-competent integrated proviral DNA can persist
for decades as HIV-1 infected cells have an average half-life close to 44 months and could be responsible for
accelerated aging. Also, despite all cART’s achievements, it’s poor penetrance across the blood-brain barrier
leads to continuous low-level viral replication in the central nervous system (CNS) could be the cause of
premature aging in PLWH. Thus, deciphering how much ART-mediated viral suppression affects aging and the
brain immune homeostasis will provide clue to understand the mechanism involved in accelerated aging in
PLWH and ultimately its therapeutic targeting. Defining the consequence of latent HIV-1 burden in the human
brain during progressive aging is limited by sample access. We plan to answer this above question by deploying
a small animal model of HIV-1 disease (NSG-humanized mice). Recently we employed NSG-humanized mice
and demonstrated recovery of latent viruses from whole brain cells. Based on these findings and new preliminary
data, we now propose to study progressive aging associated changes during HIV-infection in a long-term
immune reconstituted humanized mouse model. How much HIV-1 latency and cART contribute to premature
aging (we termed as LAAGING) and functional neuro-immune interaction at molecular and behavioral level will
be answered. By employing the proposed animal model under highly suppressive cART treatment, the brain
cells carrying the latent HIV-1 will be evaluated and characterized by transcriptomics and metabolic profiling.
This will be followed by measurement of axonal fiber integrity using diffusion tensor imaging and behavior
analysis to look for brain functional deficits during progressive aging. The outcome of the project will provide
valuable information for the identification of new biomarkers of aging, assessment and monitoring of combination
therapies for elimination of virus and its associated neuroinflammation in the CNS. Data from these ART-
suppressed humanized mice brain studies will also provide the first-hand evidence of the existence of neuro-
immune crosstalk both within and outside of CNS during progressiv...

## Key facts

- **NIH application ID:** 11170144
- **Project number:** 1R56AG087827-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Prasanta Kumar Dash
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $383,750
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11170144

## Citation

> US National Institutes of Health, RePORTER application 11170144, Exploring the Molecular, Neuro-immune and Behavioral changes during HIV-associated progressive aging using a long-term humanized mice model (1R56AG087827-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11170144. Licensed CC0.

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