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Epstein-Barr nuclear antigen 1 (EBNA1) is a multifunctional DNA-binding protein encoded by the Epstein-Barr virus (EBV), essential for viral genome replication, episome maintenance during latency, and partitioning in host cells.[2][3][6] It binds specific elements like the dyad symmetry (DS) and family of repeats (FR) in the viral origin of replication (oriP), ensuring persistent infection in B cells and epithelial cells.[3][5] EBNA1 is uniquely expressed across all EBV-associated cancers, including Burkitt's lymphoma, Hodgkin's lymphoma, gastric carcinoma, and nasopharyngeal carcinoma, where it drives tumorigenesis by supporting viral persistence and host cell survival.[2][5] In SLE and autoimmune contexts, related EBV antigens like EBNA2 reprogram infected B cells for enhanced antigen presentation, but EBNA1's role centers on latency.[1] Small-molecule inhibitors targeting EBNA1's DNA-binding domain, such as 2,3-disubstituted benzoic acids, selectively block latent infection, suppress EBV transcription, and inhibit tumor growth in xenografts, including patient-derived models, with favorable pharmacology.[2] These advances position EBNA1 as a promising antiviral and anticancer target, though long-term effects on TGF-β pathways require further study.[2]
Inhibition of EBNA1 DNA binding, blocking viral latent infection, EBV gene transcription, and tumor growth
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