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

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 ( lncBART s). The exact roles lncBART s in the EBV life cycle and the development of EBV‐associated cancers are largely not understood. This study demonstrates that lncBART s play a role in maintaining viral genome replication by affecting the tethering of EBV ori P region to chromosome. Mechanistically, lncBART s 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 ori P to facilitate EBV episome replication. Additionally, the lncBART s‐BRD4/CTCF complex contributes to the regulation of MYC and BCL2 expression. These findings suggest that lncBART s modulate EBV latency through interactions with ori P region, while lncBART s‐BRD4/CTCF complexes promote host epigenome reprogramming and drive tumorigenesis in EBV‐associated epithelial tumors.