EBNA1

Epstein-Barr virus nuclear antigen 1 (EBNA1) is a latent-phase protein of Epstein-Barr virus (EBV) that is essential for the maintenance and replication of the viral genome as an episome in infected B cells. It is the only EBV nuclear antigen consistently expressed across all latency programs, making it a central factor in persistent EBV infection and associated diseases.

EBNA1 is a DNA-binding protein that recognizes the origin of replication, oriP, which comprises two functional elements: the dyad symmetry (DS) element and the family of repeats (FR). EBNA1 functions as a dimer and binds DS to mediate replication of the episome, while FR serves as a transcriptionally active region rich in EBNA1 binding sites. The C-terminal domain of EBNA1 provides a nuclear localization signal and mediates chromatin association, enabling the viral genomes to tether to host chromosomes during mitosis so that they are equally partitioned to daughter cells.

A distinct feature of EBNA1 is its glycine-alanine repeat (GAr) region in the N-terminus, which reduces proteasomal processing and subsequent presentation by MHC class I molecules. This motif contributes to immune evasion by limiting detection of EBNA1-derived peptides by CD8+ T cells, aiding in the long-term persistence of EBV-infected cells.

Beyond episome maintenance, EBNA1 also influences transcriptional regulation near oriP and interacts with host factors to modulate viral and cellular gene expression. Due to its indispensable role in EBV latency, EBNA1 is a focus of research into therapeutic strategies targeting persistent EBV infections and EBV-associated malignancies.