# Epigenetics of dysfunctional oral epithelium in people living with HIV and risk for HPV infection

> **NIH NIH R21** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $195,375

## Abstract

With the increase in life expectancy of people living with HIV (PLWH), principally due to the introduction of
antiretroviral therapy (ART), it has become evident that these individuals differentially acquire a wide range
of health problems, including oral health complications, which severely impact quality of life and incur
substantial healthcare costs. We previously identified an altered proteomic profile of human oral
keratinocytes isolated from PLWH patients, suggesting elevated cellular stress and reduced ability to
provide robust innate immune protection. We also demonstrated that these epithelial cells display altered
epigenetic markers, reduced proliferative capacity and respond weakly to microbial challenges.
We now hypothesize that in PLWH, oral epithelial cell dysfunction predisposes towards
susceptibility to secondary viral infections, such as HPV. We have assembled an interdisciplinary
team of experts whose expertise encompasses HIV and HPV virology, oral and epithelial cell biology,
epigenomics and bioinformatics. We propose to apply a novel non-invasive method of collecting oral
mucosal cells from PLWH and conduct genomic and epigenomic analyses of the oral epithelium (Aim 1).
Additionally, using a relevant HPV infection model, we wish to determine if such cells expanded from the
oral mucosa of PLWH, which we have demonstrated exhibit an altered proteome, are more susceptible to
HPV infection when compared to oral epithelial cells from healthy controls (Aim 2). These studies will be
the first to establish the transcriptomic and epigenomic effects of HIV infection on primary epithelial cells,
establish a new culture-based assay system so critical for future mechanistic and therapeutic studies, and
enable direct comparisons between these in vivo and in vitro methods to robustly identify key molecular
features that are central to the increased HPV susceptibility seen in PLWH.
Successful completion of the goals of this R21 will enable targeted hypothesis-based genomic or
epigenomic studies (i.e. shRNAs, CRISPR, or small molecules) to identify specific genes/pathways
mediating the HPV susceptibility, and functionally test HPV infection levels. Validating the epigenetic basis
of susceptibility to HPV infection in PLWH will eventually guide the discovery and application of novel
epigenomic-based clinical interventions; all consistent with the goals of the NOSI NOT-DE-21-019 “Basic
and translational oral health research related to HIV/AIDS.”

## Key facts

- **NIH application ID:** 10880690
- **Project number:** 5R21DE032626-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** AARON WEINBERG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,375
- **Award type:** 5
- **Project period:** 2023-07-03 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880690

## Citation

> US National Institutes of Health, RePORTER application 10880690, Epigenetics of dysfunctional oral epithelium in people living with HIV and risk for HPV infection (5R21DE032626-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10880690. Licensed CC0.

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