# Targeting Epstein-Barr Virus Super-Enhancer

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $447,500

## Abstract

Epstein-Barr Virus (EBV) causes infectious mononucleosis, lymphomas and lymphoproliferative
diseases in HIV infected and immune suppressed people and is linked to autoimmune diseases.
EBV converts Resting B Lymphocytes (RBLs) to continuously proliferating Lymphoblasts Cell
Lines (LCLs) by expressing EBV nuclear antigens (ENBAs) and latent membrane protein 1 (LMP1)
that activates NF-kB. Since LCLs express that same EBV proteins as some EBV cancers, EBV
conversion of RBLs to LCLs is therefore a relevant model that can be genetically manipulated to
investigate EBV's role in growth transformation. LCL growth depends on EBNA2, EBNALP,
EBNA3A, EBNA3C and LMP1. Recently, we found that all the essential EBNAs and LMP1
activated NF-kB subunits converge to EBV super-enhancers (ESE) that have extraordinary
H3K27ac signals. ESEs govern the expression of key oncogenes that drive LCL growth and are
more sensitive to perturbations that average enhancers. To further characterize the molecular
composition and their functional roles in ESEs, we will (1) Determine the mechanisms through
which ESEs loop to their target genes, (2) Determine the ESE proteomic composition and identify
proteins that determine ESE formation, and (3) Determine the functional roles of ESE enhancer
RNA (eRNA). We will use Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)
based assays to identify the DNA elements essential for ESE to loop to their direct target genes
and proteins essential for ESE activity. We will test the effect of eRNA knock down on host
transcription and looping factor DNA binding. The experiments here in use integrative approaches
to elucidate the molecular mechanism by which ESEs activate key oncogenic divers. These
studies will identify opportunities for therapeutic intervention.

## Key facts

- **NIH application ID:** 10808909
- **Project number:** 5R01AI123420-09
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Bo Zhao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $447,500
- **Award type:** 5
- **Project period:** 2016-03-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808909

## Citation

> US National Institutes of Health, RePORTER application 10808909, Targeting Epstein-Barr Virus Super-Enhancer (5R01AI123420-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10808909. Licensed CC0.

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