# The role of Vpr-mediated cell cycle dysregulation in HIV-associated kidney disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $779,195

## Abstract

PROJECT SUMMARY
With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy
(HIVAN) has dramatically decreased in the recent years. Yet, the prevalence of chronic kidney disease (CKD)
and end-stage kidney disease in patients living with HIV remains high, suggesting that HIV predisposes
patients to increased risk for chronic kidney disease. Indeed, several lines of evidence from recent
epidemiological and animal model studies indicate that concurrent HIV infection and age-related comorbidities,
such as diabetes mellitus, have a synergistic effect on the incidence of chronic kidney disease, thereby
necessitating an examination of mechanisms by which HIV infection even at low viral load accelerates the
progression of CKD. Among the HIV-1 viral proteins, we previously showed that HIV viral protein R (Vpr) can
induce cell cycle dysregulation, apoptosis, and polyploidy in renal tubular cells. However, the importance and
consequences of Vpr-mediated cell cycle arrest and polyploidy has not been fully explored in the setting of
kidney disease. In this proposal, we will further dissect the mechanisms dictating the cell fates of Vpr-
expressing renal tubular using in vitro approaches (Aim 1). Similarly, using transgenic mice expressing Vpr in
renal tubular epithelial cells, we will characterize the cell cycle dysregulation and gene expression at single-cell
levels, and determine whether the pharmacological intervention of cell cycle dysregulation can attenuate
kidney disease progression in this model, as well as in HIVAN mouse model, Tg26 (Aim 2). To complement the
findings in Aims 1 and 2, we will assess the expression of genes and cell cycle regulators in kidney biopsy
samples of HIV+ CKD patients (Aim 3). We will also perform transcriptomic profiling for comparative analyses
with findings in murine kidneys. Our results will provide a better understanding of the underlying molecular
mechanisms by which chronic HIV infection accelerates the progression of CKD and a proof-of-concept for
novel target treatment for CKD in HIV patients.

## Key facts

- **NIH application ID:** 10527702
- **Project number:** 1R01DK133912-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** John Cijiang He
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $779,195
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527702

## Citation

> US National Institutes of Health, RePORTER application 10527702, The role of Vpr-mediated cell cycle dysregulation in HIV-associated kidney disease (1R01DK133912-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10527702. Licensed CC0.

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