Abstract
Epstein–Barr virus (EBV) is an etiological agent of a number of human benign and malignant tumors, including infectious mononucleosis (IM), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), non-Hodgkin lymphomas (NLHs), nasopharyngeal carcinoma (NPC), among others. Latent membrane protein 1 (LMP1) encoded by the gene of the same name (LMP1) is the main oncoprotein of EBV. LMP1 is a transmembrane protein capable of activating many signaling pathways and transcription factors of the cell, which leads to its transformation. Molecular analysis of LMP1 of various clinical origins identified many gene variants with different types of mutations that are the causes of the change in its biological activity. Since the role of LMP1 in the development of NPC is still not fully understood, it was important to determine the difference between LMP1 samples from patients with EBV-associated forms of NPC and patients with other tumors also located in the oral cavity (OTOC) not associated with this virus. In contrast a single works of this kind conducted in endemic regions, the present work aimed at a comparison of the genetic structure and transforming activity of LMP1 variants from NPC and OTOC patients was carried out in a nonendemic region, Russia, where NPC is rarely diagnosed. The obtained data show the structural and functional similarity of LMP1 variants in two groups of patients and, therefore, the genetic relationship of EBV strains persisting in these patients. Our work suggests that there is no special virus variant that causes NPC in nonendemic regions: any EBV strain with any LMP1 structure may, it seems, become the etiological agent of NPC. However, according to the modern understanding, cancer may develop in EBV-infected persons only given the presence of a unique HLA pattern associated with a high sensitivity to the NPC development combined with exposure to harmful environmental factors, which contribute to the accumulation of a certain number of mutations necessary for EBV-associated initiation of carcinogenesis in infected epithelial cells.
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Original Russian Text © N.B. Senyuta, K.V. Smirnova, S.V. Diduk, E.V. Goncharova, L.N. Shcherbak, V.E. Gurtsevitch, 2016, published in Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya, 2016, No. 2, pp. 71–75.
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Senyuta, N.B., Smirnova, K.V., Diduk, S.V. et al. Structural and functional characteristics of the LMP1 oncogene in patients with tumors аssociated and not associated with the Epstein–Barr virus. Mol. Genet. Microbiol. Virol. 31, 87–93 (2016). https://doi.org/10.3103/S0891416816020099
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DOI: https://doi.org/10.3103/S0891416816020099