# Tumorigenesis by the Epstein Barr Virus

> **NIH NIH P01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $347,155

## Abstract

Project 4
Project Summary Abstract
The goal of this project is to continue to determine how EBV modulates cell growth with particular focus on the
BART long noncoding RNAs and to identify potential effects of the presence of EBV infected cells on the
growth and expression of HPV infected cells. We have previously shown profound effects of the viral
oncogenes, latent membrane proteins 1 and 2, on the growth of cells through activation of distinct signaling
pathways and effects on protein levels through ubiquitination and determined that these proteins are secreted
in exosomes and can be transferred to uninfected cells. Recently, we have utilized RNASeq to analyze total
cellular expression in the AGS epithelial cell line, with or without EBV infection, grown in vitro and as tumors in
NOD SCID mice in comparison with the C666 NPC cell line, and the NPC xenografts C15 and C17. The
majority of the identified canonical pathways based on two fold changes in expression had decreased activity
in vivo. EBV expression was also distinct with greatly increased transcription of the BART non coding RNAs in
both NPC and the AGS cells. The significant expression of the viral BART nc RNAs in vivo in the absence of
the EBV transforming proteins suggests that they are contributing factors to tumorigenesis. Their effects and
potential mechanisms of action are a major focus of this application.
EBV persistent infection in the oropharynx has several states of infection with cells that express multiple viral
proteins including LMP1 and LMP2, cells that are restricted to BART miRNA and lnc RNA, and cells with some
replicative reactivation. It is likely that through EV shedding, EBV may greatly impact other oropharyngeal viral
infections. Importantly, HPV throat cancer is now the most rapidly increasing virally associated cancer. The
almost universal oral infection with EBV could likely modulate the growth and cellular expression of HPV
infected cells and potentially enhance their oncogenic properties. The in vivo interactions of EBV and HPV
have not yet been defined. This proposal will determine how the distinct latent EBV infections or permissive
infection alter the growth and expression of HPV infected cells.

## Key facts

- **NIH application ID:** 10495576
- **Project number:** 2P01CA019014-42A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** NANCY JOAN RAAB-TRAUB
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,155
- **Award type:** 2
- **Project period:** 1997-05-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495576

## Citation

> US National Institutes of Health, RePORTER application 10495576, Tumorigenesis by the Epstein Barr Virus (2P01CA019014-42A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10495576. Licensed CC0.

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