Epstein-Barr nuclear antigen 3 (EBNA3)

Epstein-Barr nuclear antigen 3 (EBNA3) refers to a family of three large viral proteins—EBNA3A, EBNA3B, and EBNA3C—that are expressed during the latent phase of Epstein-Barr virus (EBV) infection [1, 2]. These proteins are essential for the virus's ability to persist in B lymphocytes and are primary drivers of B-cell transformation into immortalized lymphoblastoid cell lines [2, 3]. EBNA3A and EBNA3C act as oncoproteins by transcriptionally repressing host tumor suppressors, such as the cyclin-dependent kinase inhibitor p16INK4A and the pro-apoptotic protein BIM, thereby promoting cell cycle progression and survival [3, 4]. Conversely, EBNA3B functions as a viral tumor suppressor that modulates the host immune response and restrains excessive cell proliferation [1, 2]. As highly immunogenic proteins, the EBNA3 family members are major targets for the host's cytotoxic T-lymphocyte (CTL) response, which is critical for controlling EBV-associated malignancies [10, 16]. This immunogenicity has been exploited in the development of adoptive T-cell therapies, such as tabelecleucel, which uses EBV-specific T cells to target and eliminate infected cells in patients with post-transplant lymphoproliferative disorder [13, 17]. While no small-molecule inhibitors specifically targeting EBNA3 are currently approved, research continues into disrupting their interactions with cellular factors like RBP-Jκ and CtBP [18]. EBNA3 proteins are central to the pathogenesis of various diseases, including Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma [2, 11].

Other names

EBNA-3EBNA-3AEBNA-3BEBNA-3CEBNA-4EBNA-6BERF1BERF2BERF3BERF4BLRF3

Adoptive T-cell therapy utilizing EBV-specific cytotoxic T lymphocytes that recognize EBNA3-derived peptides presented by HLA molecules on the surface of infected cells, leading to targeted cell lysis.