# Role of bFGF low affinity receptors in childhood HIVAN

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $538,642

## Abstract

PROJECT SUMMARY/ABSTRACT
Most of the 2.5 million children and adolescents living with HIV-1 (CALWH) worldwide reside in Sub-Saharan
Africa. Those who carry two copies of the APOL1 risk alleles (RA) are at higher risk of developing HIV-chronic
kidney diseases (HIV-CKD) if they are not treated continuously with modern anti-retroviral therapy (ART)
throughout childhood. During the last grant cycle, we followed the outcome of ~ 200 CALWH in the Washington
DC area for an average period of 5 years, and found that many developed HIV-CKD despite ART. We also found
that children with high plasma and urine levels of the heparin binding cytokine Fibroblast Growth Factor-2 (FGF-
2), were at further risk of developing HIV-CKD, and that FGF-2 increased the renal recruitment and attachment
of HIV+ cells in mice. Thus, we hypothesize that FGF-2 release into the circulation accelerates the progression
of childhood HIV-CKD, acting in synergy with the APOL1-RA and other HIV proteins, by facilitating the renal
recruitment of HIV-infected cells, as well as the infection and/or injury of renal cells despite ART. We further
hypothesize that FGF-2 precipitates the detachment of viable podocytes and tubular epithelial cells (REc), and
that the phenotype and transcriptome profiles of these cells can be used to distinguish CALWH undergoing
HIVAN and/or other progressive HIV-CKD, and to follow their outcome in a non-invasive manner. This hypothesis
will be tested in three aims. In aim 1, we will define how FGF-2 and APOL1-RA interact to precipitate HIV-CKDs
in CALWH on ART, and define the clinical value of single cell urinary transcriptome profiles to distinguish CALWH
undergoing HIVAN and/or other progressive HIV-CKD. In aim 2, we will determine how FGF-2 and APOL1-RA
interact to modulate the infection, injury, and/or survival of HIV-infected cells cultured from children with HIV-
CKD. In aim 3, we will use two new mouse models of childhood HIV-CKD, to determine how FGF-2 interacts
with APOL1-RA and HIV-Nef to precipitate the detachment of podocytes/REc and accelerate the progression of
HIV-CKD. In addition, we will identify the most relevant signaling pathways involved in these processes, and
define how drugs that block the selected pathways affect the progression of HIV-CKD in young mice.

## Key facts

- **NIH application ID:** 10876899
- **Project number:** 5R01DK049419-22
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** PATRICIO E. RAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $538,642
- **Award type:** 5
- **Project period:** 1999-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876899

## Citation

> US National Institutes of Health, RePORTER application 10876899, Role of bFGF low affinity receptors in childhood HIVAN (5R01DK049419-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876899. Licensed CC0.

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