# Project 4 - Controlling the Latent-to-Lytic Switch in Epstein-Barr Virus

> **NIH NIH P01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $389,461

## Abstract

PROJECT 4 – PROJECT SUMMARY/ABSTRACT
Epstein-Barr virus (EBV) is associated with 2% of human cancers, including a variety of B-cell lymphomas,
nasopharyngeal carcinomas, and some gastric cancers. Over the current funding period, we developed a
new epithelial cell line infected with EBV that can be used to identify factors that regulate the switch from
latency to lytic infection that occurs during differentiation of epithelial cells. Using this and other EBV-infected
cell lines, we identified multiple cellular factors that play key roles in determining whether EBV remains
dormant or reactivates into lytic replication. We also discovered three novel classes of drugs (iron chelators,
NEDDylation inhibitors, and immunomodulatory drugs such as pomalidomide) that induce reactivation of
latent EBV into lytic replication, two of which are already FDA-approved for other uses. Based upon our
findings, we hypothesize that p53 family members and NEDDylation are key contributors to regulation of the
EBV latent-to-lytic switch. Here, we propose to test this hypothesis by determining: (i) the roles played by p53
(the most commonly mutated protein in cancers) and its close family member, ΔNp63, in regulating EBV’s life
cycle during differentiation of EBV-infected epithelial cells and treatment of these cells with drugs that induce
lytic EBV replication; and (ii) how the NEDDylation inhibitor, MLN4924, and the iron chelator, deferoxamine,
induce lytic EBV replication in cells latently infected with this virus. The information obtained from these
experiments will then be used to identify optimal combinations of these drugs, together with other FDA-
approved drugs, for efficiently inducing EBV into lytic infection in cancer cells in which it is latent. We are
hopeful that these studies will lead to new lytic-induction therapies for treating patients with EBV-associated
cancers.

## Key facts

- **NIH application ID:** 10149958
- **Project number:** 5P01CA022443-44
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Janet Elaine Mertz
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $389,461
- **Award type:** 5
- **Project period:** 1997-02-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149958

## Citation

> US National Institutes of Health, RePORTER application 10149958, Project 4 - Controlling the Latent-to-Lytic Switch in Epstein-Barr Virus (5P01CA022443-44). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149958. Licensed CC0.

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