Epstein-Barr virus nuclear antigen 1 (EBNA1)

Epstein-Barr virus nuclear antigen 1 (EBNA1) is a multifunctional dimeric protein that is indispensable for the persistence, replication, and segregation of the Epstein-Barr virus (EBV) genome within host cells [6, 11, 23]. It functions as a sequence-specific DNA-binding protein that tethers the viral episome to host chromosomes during mitosis, ensuring stable maintenance of the viral genome [23]. EBNA1 is the only viral protein consistently expressed in all EBV-associated malignancies, including nasopharyngeal carcinoma, Burkitt lymphoma, and EBV-positive gastric cancer, where it facilitates viral latency and cell survival [9, 19, 20]. Beyond its oncogenic roles, EBNA1 has been critically linked to the etiology of multiple sclerosis (MS) through molecular mimicry, as antibodies generated against EBNA1 can cross-react with central nervous system proteins such as GlialCAM [15, 18]. Because EBNA1 possesses a unique protein fold with no known human orthologs, it represents a highly selective therapeutic target [4, 9]. Current clinical development focuses on small-molecule inhibitors like VK-2019, which aim to disrupt the EBNA1-DNA interaction, thereby inducing the loss of the viral genome and inhibiting the growth of EBV-dependent tumors [1, 5, 8].

Other names

EBNA-1BKRF1 proteinEBV nuclear antigen 1Epstein-Barr nuclear antigen 1

Small-molecule inhibitors target the EBNA1 DNA-binding domain or dimerization interface to disrupt sequence-specific binding to the viral origin of plasmid replication (oriP), thereby preventing viral episome maintenance, genome replication, and the expression of viral oncogenes.