# Tumor suppressor reprogramming by EBV through post-translational modification

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $539,377

## Abstract

Abstract:
Immunocompromised HIV-positive patients have serious complications with opportunistic
oncogenic viral infections that can lead B-cell lymphomas. Epstein-Barr virus (EBV) and
Kaposi’s sarcoma associated virus (KSHV) are two human oncogenic gammaherpesviruses
associated with B-cell lymphomas either individually or as co-infections. EBV-associated B-cell
lymphomas are established as latency III infection with the major latent genes expressed as well
as the small non-coding RNAs. EBV transformed B cells drive latency III, also seen in HIV
associated EBV-positive lymphomas. EBV is also associated with other lymphomas including
Burkitt’s lymphoma, Hodgkin’s and non-Hodgkin’s lymphoma, and post-transplant and AIDS
associated lymphomas in immunocompromised HIV-patients. EBV also efficiently transforms
human primary B-cells in vitro, into immortalized lymphoblastoid cell lines (LCLs). These
nascent transformed B cells express latent genes, one of which is the Epstein-Barr nuclear
antigen EBNA3C, essential for immortalization of B-cells. EBNA3C regulates cellular and viral
gene expression through interaction with transcription repressors, and complexes of the
mammalian cell cycle which include CyclinA, and components of the SCF proteosome
degradation pathway. Our long term goal is to determine the role of EBNA3C in reprogramming
viral and infected cell genomes through interactions with the tumor suppressor Rb and the
regulatory consequences of these interactions as related to cell survival, cell cycle regulation
and proliferation. We will investigate the mechanism of Rb regulation through specific post-
translation modifications after infection by EBV, which includes phosphorylation and acetylation
important for targeted ubiquitination. We will determine if enhanced phosphorylation/acetylation
of Rb occurs through recruitment of CyclinD/Cdk4/6 complexes by EBNA3C important for cell
cycle progression. This results in loss of Rb through ubiquitination which leads to cell and viral
genome reprogramming by activation of the cellular E2F pathway, cell cycle progression,
increased survival and malignant transformation. These studies will examine the role of
EBNA3C in regulating the Rb/CyclinD/E2F network important for B-cell immortalization with
implications for novel insights into KSHV and EBV contributions to latency III lymphomas in HIV
patients.

## Key facts

- **NIH application ID:** 10402055
- **Project number:** 1R01CA268998-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** ERLE S. ROBERTSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $539,377
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402055

## Citation

> US National Institutes of Health, RePORTER application 10402055, Tumor suppressor reprogramming by EBV through post-translational modification (1R01CA268998-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10402055. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*