# Epstein‐Barr Virus Expressed Long Non‐Coding RNA (lncBARTs) Regulate EBV Latent Genome Replication

## TL;DR

This study shows that Epstein-Barr virus produces long non-coding RNAs (lncBARTs) that help the virus replicate and contribute to cancer development.

## Contribution

The study reveals that lncBARTs regulate EBV genome replication and promote tumorigenesis by interacting with host and viral proteins.

## Key findings

- LncBARTs tether the EBV oriP region to host chromosomes, aiding viral replication.
- LncBARTs form a complex with BRD4, CTCF, and EBNA1 to regulate viral and host gene expression.
- The lncBARTs-BRD4/CTCF complex alters proto-oncogene expression, driving tumor formation.

## Abstract

Epstein‐Barr virus (EBV) is a ubiquitous human virus that is also linked to various human cancers. In EBV‐associated nasopharyngeal carcinoma and gastric carcinoma cells, EBV expresses only essential viral antigens but high levels of long non‐coding RNAs known as BamHI‐A rightward transcripts (lncBARTs). The exact roles lncBARTs in the EBV life cycle and the development of EBV‐associated cancers are largely not understood. This study demonstrates that lncBARTs play a role in maintaining viral genome replication by affecting the tethering of EBV oriP region to chromosome. Mechanistically, lncBARTs interact functionally with a complex consisting of Bromodomain‐containing protein 4 (BRD4), CCTC‐binding factor (CTCF), and EBV nuclear antigen 1 (EBNA1), anchoring their binding at oriP to facilitate EBV episome replication. Additionally, the lncBARTs‐BRD4/CTCF complex contributes to the regulation of MYC and BCL2 expression. These findings suggest that lncBARTs modulate EBV latency through interactions with oriP region, while lncBARTs‐BRD4/CTCF complexes promote host epigenome reprogramming and drive tumorigenesis in EBV‐associated epithelial tumors.

EBV produces abundant level of lncBARTs, which are essential for maintaining viral genome replication in EBV‐associated cancers. LncBARTs interact with a complex comprising BRD4, CTCF and viral protein EBNA1 at EBV oriP region. This interaction tethers oriP to host chromosomes, facilitating EBV episome replication. Additionally, lncBARTs‐BRD4 complex alters the expression of proto‐oncogenes including MYC and BCL2 to drive tumorigenesis.