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Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2) are essential viral proteins that facilitate the persistence and oncogenic potential of EBV in host cells [1, 3]. EBNA1 is a multifunctional DNA-binding protein required for the replication, maintenance, and mitotic segregation of the EBV episomal genome, and it is the only viral protein consistently expressed in all EBV-associated malignancies [5, 10]. LMP2, which includes isoforms LMP2A and LMP2B, acts as a molecular mimic of the B-cell receptor (BCR), providing constitutive survival signals that allow infected B cells to bypass normal apoptotic checkpoints [15, 18]. These antigens are co-expressed in several EBV-related diseases, such as nasopharyngeal carcinoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorders, making them primary targets for therapeutic vaccines and adoptive T-cell therapies [2, 6, 9]. Current therapeutic strategies include small molecule inhibitors like VK-2392 that disrupt EBNA1-DNA binding and viral vector vaccines such as MVA-EBNA1/LMP2 designed to elicit robust cytotoxic T-cell responses [7, 9]. However, drug development is complicated by EBNA1's intrinsic immune evasion mechanisms, such as its Gly-Ala repeat domain, and the risk of cross-reactivity with host proteins in autoimmune conditions like multiple sclerosis [13, 18, 19].
Inhibition of viral DNA binding and episome maintenance; Induction of antigen-specific cytotoxic T-lymphocyte (CTL) responses against EBV-infected cells; Disruption of viral transcriptional regulation.
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