Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press83910.17650/2313-805X-2026-13-1-30-45REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИReview ArticleMolecular genetic factors of oncogenesis associated with the Epstein–Barr virusМолекулярно-генетические факторы онкогенеза, ассоциированного с вирусом Эпштейна–Баррhttps://orcid.org/0000-0003-3965-203355386076100AAF-7673-20208457-3501SakharnovNikolay A.СахарновНиколай Александрович
Russian Federation
sakharnov_n@mail.ruhttps://orcid.org/0000-0002-7571-525XUtkinOleg V.УткинОлег Владимирович
Russian Federation
utkino2004@mail.ruhttps://orcid.org/0009-0008-1051-882XDmitrievSergey P.ДмитриевСергей Павлович
Russian Federation
sergei-fcsm@yandex.ruhttps://orcid.org/0000-0002-6683-7191FilatovaElena N.ФилатоваЕлена Николаевна
Russian Federation
el.filatova83@mail.ruhttps://orcid.org/0000-0003-1037-2601ZinovievSvyatoslav V.ЗиновьевСвятослав Владимирович
Russian Federation
swet.ssk@yandex.ruhttps://orcid.org/0009-0006-1407-6884SuslovNikita A.СусловНикита Алексеевич
Russian Federation
suslovnikita98gr@gmail.comhttps://orcid.org/0000-0002-0223-0753GamayunovSergey V.ГамаюновСергей Викторович
Russian Federation
gamajnovs@mail.ruAcademician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Rospotrebnadzor (Russian Federal Consumer Rights Protection and Human Health Control Service)ФБУН «Нижегородский научно-исследовательский институт эпидемиологии и микробиологии им. акад. И.Н. Блохиной» РоспотребнадзораAcademician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology, Federal Service for the Oversight of Consumer Protection and WelfareФБУН «Нижегородский научно-исследовательский институт эпидемиологии и микробиологии им. акад. И.Н. Блохиной» РоспотребнадзораResearch Institute of Clinical Oncology “Nizhny Novgorod Regional Clinical Oncology Dispensary”ГАУЗ НО «Научно-исследовательский институт клинической онкологии “Нижегородский областной клинический онкологический диспансер”»16032026131304512122025Copyright ©; 2026, Sakharnov N.A., Utkin O.V., Dmitriev S.P., Filatova E.N., Zinoviev S.V., Suslov N.A., Gamayunov S.V.Copyright ©; 2026, Сахарнов Н.А., Уткин О.В., Дмитриев С.П., Филатова Е.Н., Зиновьев С.В., Суслов Н.А., Гамаюнов С.В.2026Sakharnov N.A., Utkin O.V., Dmitriev S.P., Filatova E.N., Zinoviev S.V., Suslov N.A., Gamayunov S.V.Сахарнов Н.А., Уткин О.В., Дмитриев С.П., Филатова Е.Н., Зиновьев С.В., Суслов Н.А., Гамаюнов С.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/839

Epstein–Barr virus (EBV) is a human herpesvirus type 4, which is carried by the majority of the world’s population. Its etiologic role in the development of various lymphomas, nasopharyngeal cancer, gastric cancer, and other malignancies has been proven. The mechanisms and participants of EBV-associated oncogenesis are actively studied. This review describes the molecular genetic diversity of EBV associated with the development of cancer. A literature review revealed that EBV is characterized by high structural and functional diversity of nucleotide and amino acid sequences. Based on polymorphism of EBV genes EBNA-1, EBNA-2, EBNA-LP, EBER, BZLF1, LMP-2A and LMP-1, various mutations, types, and variants, associated with malignant transformation and the development of various cancer types were identified.

Aim. To summarize and analyze literature data devoted to the study of the genetic diversity of EBV for the prospective development of molecular biological research methodology in clinical practice, as well as the development of diagnostic tools, specific prevention and therapy of EBV-associated oncological diseases based on the products of the viral genome.

Вирус Эпштейна–Барр (ВЭБ) является герпесвирусом человека 4-го типа, носительство которого характерно для большинства мирового населения. Доказана этиологическая роль ВЭБ в развитии различных лимфом, рака носоглотки, желудка и других злокачественных новообразований. Активно изучаются механизмы и участники ВЭБ-ассоциированного онкогенеза. В настоящем обзоре описывается молекулярно-генетическая вариативность ВЭБ, связанная с развитием онкологических заболеваний. Анализ литературы показал, что для этого вируса характерно высокое структурно-функциональное разнообразие нуклеотидных и аминокислотных последовательностей. На основе полиморфизма генов EBNA-1, EBNA-2, EBNA-LP, EBER, BZLF1, LMP-2A и LMP-1 выявлены различные мутации, типы и варианты генов ВЭБ, ассоциированные со злокачественной трансформацией и развитием различных типов рака.

Цель работы – обобщение и анализ данных литературы, посвященной изучению генетического разнообразия ВЭБ для перспективного развития методологии молекулярно-биологических исследований, а также разработке средств диагностики, специфической профилактики и терапии ВЭБ-ассоциированных онкологических заболеваний на основе продуктов генома вируса.

Epstein–Barr virusoncogenesisLMP-1nasopharyngeal cancerEpstein–Barr virus specific therapyвирус Эпштейна–БарронкогенезLMP-1рак носоглоткиспецифическая терапия вируса Эпштейна–БаррThe work was carried out within the framework of the Industry research program of Rospotrebnadzor for the period 2026–2030 “Scientific support for the management of the epidemic process of socially significant, especially dangerous infections and the biosecurity of the state based on genomic epidemiological surveillance, synthetic biology and digital technologies” (paragraph 1.3.3).Работа выполнена в рамках Отраслевой научно-исследовательской программы Роспотребнадзора на период 2026–2030 гг. «Научное обеспечение управления эпидемическим процессом социально-значимых, особо опасных инфекций и биобезопасности государства на основе геномного эпидемиологического надзора, синтетической биологии и цифровых технологий» (п. 1.3.3).Epstein M.A., Achong B.G., Barr Y.M. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964;1(7335):702–3. DOI: 10.1016/s0140-6736(64)91524-7Kanda T., Yajima M., Ikuta K. Epstein–Barr virus strain variation and cancer. Cancer Sci 2019;110(4):1132–9. DOI: 10.1111/cas.13954Crawford D.H. Biology and disease associations of Epstein–Barr virus. Philos Trans R Soc Lond B Biol Sci 2001;356(1408):461–73 DOI: 10.1098/rstb.2000.0783Yakushina S.A., Kisteneva L.B. Influence of the Epstein–Barr virus persistence upon the development of the immune-mediated somatic diseases. Rossiyskiy vestnik perinatologii i pediatrii = Russian Bulletin of Perinatology and Pediatrics 2018;63(1):22–7. (In Russ.). DOI: 10.21508/1027-4065-2018-63-1-22-27Якушина С.А., Кистенева Л.Б. Влияние персистенции вируса Эпштейна–Барр на развитие иммуноопосредованных соматических заболеваний. Российский вестник перинатологии и педиатрии 2018;63(1):22–7. DOI: 10.21508/1027-4065-2018-63-1-22-27Epstein–Barr virus and Kaposi’s sarcoma herpesvirus/human herpesvirus 8. Lyon (FR): International Agency for Research on Cancer. 1997. 492 p.Yushchuk N.D., Shestakova I.V. Epstein–Barr virus associated with newgrowth: clinical, immunophenotypic and immuno-citomorphological characteristic (analytical review). Infectious diseases: news, opinions, education 2013;3:33–47. (In Russ.).Ющук Н.Д., Шестакова И.В. ВЭБ-ассоциированные новообразования: клиническая, иммунофенотипическая и цитоморфологическая характеристика (аналитический обзор). Инфекционные болезни: новости, мнения, обучение 2013;3:33–47.Wong Y., Meehan M.T., Burrows S.R. et al. Estimating the global burden of Epstein–Barr virus-related cancers. J Cancer Res Clin Oncol 2022;148(1):31–46. DOI: 10.1007/s00432-021-03824-yRessing M.E., van Gent M., Gram A.M. et al. Immune evasion by Epstein–Barr virus. Curr Top Microbiol Immunol 2015;391: 355–81. DOI: 10.1007/978-3-319-22834-1_12Chakravorty S., Afzali B., Kazemian M. EBV-associated diseases: current therapeutics and emerging technologies. Front Immunol 2022;13:1059133. DOI: 10.3389/fimmu.2022.1059133Xiao Q., Liu Y., Li T. et al. Viral oncogenesis in cancer: from mechanisms to therapeutics. Signal Transduct Target Ther 2025;10(1):151. DOI: 10.1038/s41392-025-02197-9Yakushina S.A., Kisteneva L.B. Epstein–Barr virus (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4): replicative strategies. Voprosy virusologii = Problems of Virology 2020;65(4):191–202. (In Russ.). DOI: 10.36233/0507-4088-2020-65-4-191-202Якушина С.А., Кистенева Л.Б. Вирус Эпштейна–Барр (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4): репликативные стратегии. Вопросы вирусологии 2020; 65(4):191–202. DOI: 10.36233/0507-4088-2020-65-4-191-202Kaira A.N., Solomai T.V., Semenenko T.A. Epidemiology and prevention of Epstein–Barr Virus infection: a textbook. Moscow: Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2022. 81 p. (In Russ.).Каира А.Н., Соломай Т.В., Семененко Т.А. Эпидемиология и профилактика Эпштейна–Барр вирусной инфекции: учеб. пособие. М.: ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, 2022. 81 с.Johannsen E.C., Kaye K.M. Epstein–Barr virus (infectious mononucleosis, Epstein–Barr virus-associated malignant diseases, and other diseases). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 7th edn. Philadelphia: Elsevier, 2010. Pp. 1989–2010. DOI: 10.1016/B978-0-443-06839-3.00139-9Unger E., Purtilo D.T. Epstein–Barr virus and human diseases. Pathology of infectious diseases. Ed. by D.H. Connor, F.W. Chandler, H.J. Manz et al. Stamford: Appleton and Lange, 1997. Pp. 113–123.Rezk S.A., Weiss L.M. Epstein–Barr virus-associated lymphoproliferative disorders. Hum Pathol 2007;38(9):1293–304. DOI: 10.1016/j.humpath.2007.05.020Tran H., Nourse J., Hall S. et al. Immunodeficiency-associated lymphomas. Blood Rev 2008;22(5):261–81. DOI: 10.1016/j.blre.2008.03.009Gurtsevich V. The role of Epstein–Barr virus in human hematopoietic neoplasms. Clinicheskaya oncogematologia = Clinical oncohematology 2010;3(3):222–34. (In Russ.).Гурцевич В.Э. Роль вируса Эпштейна–Барр в онкогематологических заболеваниях человека. Клиническая онкогематология 2010;3(3):222–34.Arvin A., Campadelli-Fiume G., Mocarski E. et al. Herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge: Cambridge University Press, 2007.Baer R., Bankier A.T., Biggin M.D. et al. DNA sequence and expression of the B95-8 Epstein–Barr virus genome. Nature 1984;310:207–11.Santpere G., Darre F., Blanco S. et al. Genome-wide analysis of wild-type Epstein–Barr virus genomes derived from healthy individuals of the 1,000 Genomes Project. Genome Biol Evol 2014;6(4):846–60. DOI: 10.1093/gbe/evu054Human gammaherpesvirus 4 genomes. Available at: https://www.ncbi.nlm.nih.gov/datasets/genome/?taxon = 10376Kim S.M., Kang S.H., Lee W.K. Identification of two types of naturally-occurring intertypic recombinants of Epstein–Barr virus. Mol Cells 2006;21(2):302–7.Palser A.L., Grayson N.E., White R.E. et al. Genome diversity of Epstein–Barr virus from multiple tumor types and normal infection. J Virol 2015;89(10):5222–37. DOI: 10.1128/JVI.03614-14Weiss E.R., Lamers S.L., Henderson J.L. et al. Early Epstein–Barr virus genomic diversity and convergence toward the B95.8 genome in primary infection. J Virol 2018;92(2):e01466–17. DOI: 10.1128/JVI.01466-17Zhou L., Chen J.N., Qiu X.M. et al. Comparative analysis of 22 Epstein–Barr virus genomes from diseased and healthy individuals. J Gen Virol 2017;98(1):96–107. DOI: 10.1099/jgv.0.000699Zanella L., Riquelme I., Buchegger K. et al. A reliable Epstein–Barr virus classification based on phylogenomic and population analyses. Sci Rep 2019 8;9(1):9829. DOI: 10.1038/s41598-019-45986-3Yakovleva L.S., Senyuta N.B., Goncharova E.V. et al. Epstein–Barr virus LMP1 oncogene variants in cell lines of different origin. Molecularnaya biologia = Molecular Biology 2015;49(5):800–10. (In Russ.). DOI: 10.7868/S0026898415050213Яковлева Л.С., Сенюта Н.Б., Гончарова Е.В. и др. Варианты онкогена LMP1 вируса Эпштейна–Барр в клеточных линиях различного происхождения. Молекулярная биология 2015;49(5):800–10. DOI: 10.7868/S0026898415050213Neves M., Marinho-Dias J., Ribeiro J., Sousa H. Epstein–Barr virus strains and variations: geographic or disease-specific variants? J Med Virol 2017;89(3):373–87. DOI: 10.1002/jmv.24633Abdel-Hamid M., Chen J.J., Constantine N. et al. EBV strain variation: geographical distribution and relation to disease state. Virology 1992;190:168–75. DOI: 10.1016/0042-6822(92)91202-6Kimura H., Ito Y., Kawabe S. et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood 2012;119(3):673–86. DOI: 10.1182/blood-2011-10-381921Wegner F., Lassalle F., Depledge D.P. Coevolution of Sites under Immune Selection Shapes Epstein–Barr Virus Population Structure. Mol Biol Evol 2019;36(11):2512–21. DOI: 10.1093/molbev/msz152Fruscalzo A., Marsili G., Busiello V. et al. DNA sequence heterogeneity within the Epstein–Barr virus family of repeats in the latent origin of replication. Gene 2001;265(1–2):165–73. DOI: 10.1016/s0378-1119(01)00345-6Ba Abdullah M.M., Palermo R.D., Palser A.L. et al. Heterogeneity of the Epstein–Barr virus (EBV) major internal repeat reveals evolutionary mechanisms of EBV and a functional defect in the prototype EBV strain B95-8. J Virol 2017;91:e00920–17. DOI: 10.1128/JVI.00920-17Tierney R.J., Kao K.Y., Nagra J.K. et al. Epstein–Barr virus BamHI W repeat number limits EBNA2/EBNA-LP coexpression in newly infected B cells and the efficiency of B-cell transformation: a rationale for the multiple W repeats in wild-type virus strains. J Virol 2011;85(23):12362–75. DOI: 10.1128/JVI.06059-11Kudin A.P. This “harmless” Epstein–Barr virus infection. Part 1. Characteristics of the pathogen. The immune system’s response to the virus. Meditsinskie novosti = Medical News 2006;7:14–22. (In Russ.).Кудин А.П. Эта «безобидная» вирус Эпштейна–Барра инфекция. Ч. 1. Характеристика возбудителя. Реакция иммунной системы на вирус. Медицинские новости 2006;7:14–22.Fu Q., He C., Mao Z.R. Epstein–Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells. J Zhejiang Univ Sci B 2013;14(1):8–24. DOI: 10.1631/jzus.B1200189Bhatia K., Raj A., Guitierrez M.I. et al. Variation in the sequence of Epstein Barr virus nuclear antigen 1 in normal peripheral blood lymphocytes and in Burkitt’s lymphomas. Oncogene 1996;13(1);177–81.Habeshaw G., Yao Q.Y., Bell A.I. et al. Epstein–Barr virus nuclear antigen 1 sequences in endemic and sporadic Burkitt’s lymphoma reflect virus strains prevalent in different geographic areas. J Virol 1999;73(2):965–75. DOI: 10.1128/JVI.73.2.965-975.1999Smatti M.K., Yassine H.M., AbuOdeh R. et al. Prevalence and molecular profiling of Epstein Barr virus (EBV) among healthy blood donors from different nationalities in Qatar. PLoS One 2017;12(12):e0189033. DOI: 10.1371/journal.pone.0189033White R.E., Rämer P.C., Naresh K.N. et al. EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest 2012;122(4):1487–502. DOI: 10.1172/JCI58092Lo A.K., Dawson C.W., Jin D.Y., Lo K.W. The pathological roles of BART miRNAs in nasopharyngeal carcinoma. J Pathol 2012;227(4):392–403. DOI: 10.1002/path.4025Hui K.F., Chan T.F., Yang W. et al. High risk Epstein–Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma. Int J Cancer 2019;144(12):3031–42. DOI: 10.1002/ijc.32049Wu Y., Maruo S., Yajima M. et al. Epstein–Barr virus (EBV)-encoded RNA 2 (EBER2) but not EBER1 plays a critical role in EBV-induced B-cell growth transformation. J Virol 2007;81(20):11236–45. DOI: 10.1128/JVI.00579-07Martini M., Capello D., Serraino D. et al. Characterization of variants in the promoter of EBV gene BZLF1 in normal donors, HIV-positive patients and in AIDS-related lymphomas. J Infect 2007;54(3):298–306. DOI: 10.1016/j.jinf.2006.04.015Farrell P.J. Epstein–Barr virus strain variation. Curr Top Microbiol Immunol 2015;390(1):45–69. DOI: 10.1007/978-3-319-22822-8_4Tzellos S., Farrell P.J. Epstein–Barr virus sequence variation-biology and disease. Pathogens 2012;1(2):156–74. DOI: 10.3390/pathogens1020156Banko A.V., Lazarevic I.B., Folic M.M. et al. Characterization of the variability of Epstein–Barr virus genes in nasopharyngeal biopsies: potential predictors for carcinoma progression. PLoS One 2016;11(4):e0153498. DOI: 10.1371/journal.pone.0153498Alanazi A.E., Alhumaidy A.A., Almutairi H. et al. Evolutionary analysis of LMP-1 genetic diversity in EBV-associated nasopharyngeal carcinoma: Bioinformatic insights into oncogenic potential. Infect Genet Evol 2024;120:105586. DOI: 10.1016/j.meegid.2024.105586Smatti M.K., Al-Sadeq D.W., Ali N.H. et al. Epstein–Barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: an update. Front Oncol 2018;8:211. DOI: 10.3389/fonc.2018.00211Li S.N., Chang Y.S., Liu S.T. Effect of a 10-amino acid deletion on the oncogenic activity of latent membrane protein 1 of Epstein–Barr virus. Oncogene 1996;12(10):2129–35.Mainou B.A., Raab-Traub N. LMP1 strain variants: biological and molecular properties. J Virol 2006;80(13):6458–68. DOI: 10.1128/JVI.00135-06Kang M.S., Kieff E. Epstein–Barr virus latent genes. Exp Mol Med 2015;47(1):e131. DOI: 10.1038/emm.2014.84Zeng M.S., Li D.J., Liu Q.L. et al. Genomic sequence analysis of Epstein–Barr virus strain GD1 from a nasopharyngeal carcinoma patient. J Virol 2005;79(24):15323–30. DOI: 10.1128/JVI.79.24.15323-15330.2005Pai P.C., Tseng C.K., Chuang C.C. et al. Polymorphism of C-terminal activation region 2 of Epstein–Barr virus latent membrane protein 1 in predicting distant failure and post-metastatic survival in patients with nasopharyngeal carcinoma. Head Neck 2007;29(2):109–19. DOI: 10.1002/hed.20483Trinh C.T.H., Tran D.N., Nguyen L.T.T. et al. LMP1-EBV gene deletion mutations and HLA genotypes of nasopharyngeal cancer patients in Vietnam. Pathophysiology 2023;30(1):1–12. DOI: 10.3390/pathophysiology30010001Montes-Mojarro I.A., Fend F., Quintanilla-Martinez L. EBV and the pathogenesis of NK/T Cell Lymphoma. Cancers (Basel) 2021;13(6):1414. DOI: 10.3390/cancers13061414Smirnova K.V., Diduk S.V., Gurtsevitch V.E. Polymorphism of Epstein–Barr virus LMP1 oncogene in nanaians, representatives of indigenous minority of the Russian far East. Epidemiologiya i infektsionnye bolezni = Epidemiology and Infectious Diseases 2017;22(5):239–47. (In Russ.). DOI: 10.1882/1560-9529-2017-22-5-239-247Смирнова К.В., Дидук С.В., Гурцевич В.Э. Полиморфизм онкогена LMP1 вируса Эпштейна–Барр у представителей коренного малочисленного народа Дальнего Востока России. Эпидемиология и инфекционные болезни 2017;22(5):239–47. DOI: 10.18821/1560-9529-2017-22-5-239-247Diduk S.V., Smirnova K.V., Pavlish О.А., Gurtsevitch V.E. Functionally significant mutations in Epstein–Barr virus LMP1 gene and their role in activation of cell signaling pathways. Biochimia = Biochemistry 2008;73(10):1414–21. (In Russ.).Дидук С.В., Смирнова К.В., Павлиш О.А., Гурцевич В.Э. Роль функционально значимых мутаций гена LMP1 вируса Эпштейна–Барр в активации клеточных сигнальных путей. Биохимия 2008;73(10):1414–21.Sample J.T., Sample C.E. Epstein–Barr virus: molecular biology. In: Encyclopedia of virology. Oxford: Academic Press, 2008. Pp. 157–167.Kirchmaier A.L., Sugden B. Dominant-negative inhibitors of EBNA-1 of Epstein–Barr virus. J Virol 1997;71(3):1766–75. DOI: 10.1128/JVI.71.3.1766-1775.1997Li J.S.Z., Abbasi A., Kim D.H. et al. Chromosomal fragile site breakage by EBV-encoded EBNA1 at clustered repeats. Nature 2023;616(7957):504–9. DOI: 10.1038/s41586-023-05923-xSandvej K., Zhou X.G., Hamilton-Dutoit S. EBNA-1 sequence variation in Danish and Chinese EBV-associated tumours: evidence for geographical polymorphism but not for tumour-specific subtype restriction. J Pathol 2000;191(2):127–31. DOI: 10.1002/(SICI)1096-9896(200006)191:2< 127::AID-PATH614>3.0.CO;2-EChoi S.J., Jung S.W., Huh S. et al. Phylogenetic comparison of Epstein–Barr virus genomes. J Microbiol 2018;56:525–33. DOI: 10.1007/s12275-018-8039-xKelly G., Bell A., Rickinson A. Epstein–Barr virus-associated Burkitt lymphomagenesis selects for downregulation of the nuclear antigen EBNA2. Nat Med 2002;8(10):1098–104. DOI: 10.1038/nm758Dambaugh T., Hennessy K., Chamnankit L. et al. U2 region of Epstein–Barr virus DNA may encode Epstein–Barr nuclear antigen 2. Proc Natl Acad Sci USA 1984;81(23):7632–6. DOI: 10.1073/pnas.81.23.7632Rowe M., Young L.S., Cadwallader K. et al. Distinction between Epstein–Barr virus type A (EBNA 2A) and type B (EBNA 2B) isolates extends to the EBNA 3 family of nuclear proteins. J Virol 1989;63(3):1031–9. DOI: 10.1128/JVI.63.3.1031-1039.1989.Sample J., Young L., Martin B. et al. Epstein–Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol 1990;64(9):4084–92. DOI: 10.1128/JVI.64.9.4084-4092.1990Tsai M.H., Lin X., Shumilov A. et al. The biological properties of different Epstein–Barr virus strains explain their association with various types of cancers. Oncotarget 2017;8(6):10238–54. DOI: 10.18632/oncotarget.14380Gurtsevitch V.E., Lubenskaya A.K., Senyuta N.B., Smirnova K.V. Epstein–Barr virus (Orthoherpesviridae: Lymphocryptovirus) among Russian ethnic groups: prevalence of EBV types (EBV-1 and EBV-2), LMP1 gene variants and malignancies. Voprosy Virusologii = Problems of Virology 2024;69(1):56–64. (In Russ.). DOI: 10.36233/0507-4088-214Гурцевич В.Э., Лубенская А.К., Сенюта Н.Б., Смирнова К.В. Вирус Эпштейна–Барр (Orthoherpesviridae: Lymphocryptovirus) у этносов России: распространенность типов ВЭБ (ВЭБ-1 и ВЭБ-2), варианты гена LMP1 и злокачественные опухоли. Вопросы вирусологии 2024;69(1):56–64. DOI: 10.36233/0507-4088-214Lubenskaya A.K., Smirnova K.V., Gurtsevich V.E. Molecular markers of EBV-associated nasopharyngeal cancer in Russia. Voprosy oncologii = Issues of oncology 2023;69(3S):545–546. (In Russ.). DOI: 10.37469/0507-3758-2023-69-3s1Лубенская А.К., Смирнова К.В., Гурцевич В.Э. Молекулярные маркеры ВЭБ-ассоциированного рака носоглотки в России. Вопросы онкологии 2023;69(3S):545–6. DOI: 10.37469/0507-3758-2023-69-3s1Smirnova K.V., Lubenskaya A.K., Senyuta N.B. et al. Epstein–Barr virus (Herpesviridae: Lymphocryptovirus) types 1 and 2 and other viral markers in nasopharyngeal carcinoma patients in two geographically and ethnically different regions of Russia. Voprosy Virusologii = Problems of Virology 2023;68(4):291–301. (In Russ.). DOI: 10.36233/0507-4088-181Смирнова К.В., Лубенская А.К., Сенюта Н.Б. и др. Вирус Эпштейна–Барр 1-го и 2-го типа (Herpesviridae: Lymphocryptovirus) и другие маркеры вируса у больных раком носоглотки в двух этнически и географически отличающихся регионах России. Вопросы вирусологии 2023;68(4):291–301. DOI: 10.36233/0507-4088-181Al-Mozaini M., Bodelon G., Karstegl C.E. et al. Epstein–Barr virus BART gene expression. J Gen Virol 2009;90(2):307–16. DOI: 10.1099/vir.0.006551-0Lin X., Tsai M.H., Shumilov A. et al. The Epstein–Barr virus BART miRNA cluster of the M81 strain modulates multiple functions in primary B cells. PLoS Pathog 2015;11(12):e1005344. DOI: 10.1371/journal.ppat.1005344Sergeeva N.S., Marshutina N.V., Solokhina M.P. et al. Epstein–Barr virus-associated solid malignancies. Onkologiya. Zhurnal im. P.A. Gertsena = P.A. Herzen Journal of Oncology 2018;7(5):80–9. (In Russ.). DOI: 10.17116/onkolog2018705180Сергеева Н.С., Маршутина Н.В., Солохина М.П. и др. Ассоциированные с вирусом Эпштейна–Барр солидные злокачественные новообразования. Онкология. Журнал им. П.А. Герцена 2018;5:80–9. DOI: 10.17116/onkolog2018705180Kieff E., Rickinson A.B. Epstein–Barr virus and its replication. In: Field’s virology. Philadelphia: Lippincott Williams & Wilkins, 2007. Pp. 2603–2654.Ma S.D., Hegde S., Young K.H. et al. A new model of Epstein–Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol 2011;85(1):165–77. DOI: 10.1128/JVI.01512-10Gutiérrez M.I., Ibrahim M.M., Dale J.K. et al. Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein–Barr virus. J Natl Cancer Inst 2002;94(23):1757–63. DOI: 10.1093/jnci/94.23.1757Bristol J.A., Djavadian R., Albright E.R. et al. A cancer-associated Epstein–Barr virus BZLF1 promoter variant enhances lytic infection. PLoS Pathog 2018;14:e1007179. DOI: 10.1371/journal.ppat.1007179Tsai M.H., Raykova A., Klinke O. et al. Spontaneous lytic replication and epitheliotropism define an Epstein–Barr virus strain found in carcinomas. Cell Rep 2013;5(2):458–70. DOI: 10.1016/j.celrep.2013.09.012Swart R., Ruf I.K., Sample J. et al. Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-kinase/Akt pathway. J Virol 2000;74(22):10838–45. DOI: 10.1128/jvi.74.22.10838-10845.2000Moody C.A., Scott R.S., Amirghahari N. et al. Modulation of the cell growth regulator mTOR by Epstein–Barr virus-encoded LMP2A. J Virol 2005;79(9):5499–506. DOI: 10.1128/JVI.79.9.5499-5506.2005Wang Y., Rong Y., Yang L., Lu Z. Genetic variability and mutation of Epstein‒Barr virus (EBV)-encoded LMP-1 and BHRF-1 genes in EBV-infected patients: identification of precise targets for development of personalized EBV vaccines. Virus Genes 2023;59(4):541–53. DOI: 10.1007/s11262-023-02006-xBegic V., Korac P., Gasparov S. et al. Molecular characterisation of Epstein–Barr virus in classical Hodgkin Lymphoma. Int J Mol Sci 2022;23(24):15635. DOI: 10.3390/ijms232415635Bouvard V., Baan R., Straif K. et al. A review of human carcinogens – part B: biological agents. Lancet Oncol 2009;10 (4):321–2. DOI: 10.1016/s1470-2045(09)70096-8Fierti A.O., Yakass M.B., Okertchiri E.A. et al. The role of Epstein–Barr virus in modulating key tumor suppressor genes in associated malignancies: epigenetics, transcriptional, and post-translational modifications. Biomolecules 2022;12(1):127. DOI: 10.3390/biom12010127Dirmeier U., Neuhierl B., Kilger E. et al. Latent membrane protein 1 is critical for efficient growth transformation of human B cells by Epstein–Barr virus. Cancer Res 2003;63:2982–89.Edwards R.H., Seillier-Moiseiwitsch F., Raab-Traub N. Signature amino acid changes in latent membrane protein 1 distinguish Epstein–Barr virus strains. Virology 1999;261(1):79–95. DOI: 10.1006/viro.1999.9855Sarshari B., Mohebbi S.R., Ravanshad M. et al. Sequence variations of Epstein–Barr virus LMP1 gene in gastric cancer and chronic gastritis isolates from Iranian patients. Gastroenterol Hepatol Bed Bench 2022;15(3):225–31. DOI: 10.22037/ghfbb.v15i3.2578Goncharova E.V., Senyuta N.B., Smirnova K.V. et al. Epstein–Barr virus (EBV) in Russia: infection of the population and analysis of the LMP1 gene variants in patients with EBV-associated pathologies and healthy individuals. Voprosy virusologii = Issues of Virology 2015;60(2):11–7. (In Russ.).Гончарова Е.В., Сенюта Н.Б., Смирнова К.В. и др. Вирус Эпштейна–Барр (ВЭБ) в России: инфицированность населения и анализ вариантов гена LMP1 у больных ВЭБ-ассоциированными патологиями и здоровых лиц. Вопросы вирусологии 2015;60(2):11–7.Gurtsevich V.E., Smirnova K.V., Diduk S.V. et al. Polymorphism of the LMP1 gene in patients with EBV-negative forms of gastric cancer. Voprosy virusologii = Problems of virology 2010;55(5):29–34. (In Russ.).Гурцевич В.Э., Смирнова К.В., Дидук С.В. и др. Полиморфизм гена LMP1 у больных ВЭБ-негативными формами рака желудка. Вопросы вирусологии 2010;55(5):29–34.Walling D.M., Brown A.L., Etienne W. et al. Multiple Epstein–Barr virus infections in healthy individuals. J Virol 2003;77(11):6546–50. DOI: 10.1128/jvi.77.11.6546-6550.2003Saechan V., Mori A., Mitarnun W. et al. Analysis of LMP1 variants of EBV in Southern Thailand: evidence for strain-associated T-cell tropism and pathogenicity. J Clin Virol 2006;36(2):119–25. DOI: 10.1016/j.jcv.2006.01.018Nguyen-Van D., Ernberg I., Phan-Thi Phi P. et al. Epstein–Barr virus genetic variation in Vietnamese patients with nasopharyngeal carcinoma: full-length analysis of LMP1. Virus Genes 2008;37(2):273–81. DOI: 10.1007/s11262-008-0262-9Smirnova K.V., Senyuta N.B., Lubenskaya A.K. et al. Ancient variants of the Epstein–Barr virus (Herpesviridae, Lymphocryptovirus, HHV-4): hypotheses and facts. Voprosy Virusologii = Problems of Virology 2020;65(2):77–86. (In Russ.). DOI: 10.36233/0507-4088-2020-65-2-77-86Смирнова К.В., Сенюта Н.Б., Лубенская А.К. и др. Древние варианты вируса Эпштейна–Барр (Herpesviridae, Lymphocryptovirus, HHV-4): гипотезы и факты. Вопросы вирусологии 2020; 65(2):77–86. DOI: 10.36233/0507-4088-2020-65-2-77-86Gurtsevitch V.E., Smirnova K.V., Botezatu I.V. et al. Epstein–Barr virus LMP1 oncogene polymorphism in tatar and slavic populations in Russian Federation impacting on some malignant tumours. Infektsiya i immunitet = Russian Journal of Infection and Immunity 2020;10(2):347–58. (In Russ.). DOI: 10.15789/2220-7619-EBV-1162Гурцевич В.Э., Смирнова К.В., Ботезату И.В. и др. Полиморфизм онкогена LMP1 вируса Эпштейна–Барр в двух этнических группах России, татар и славян, и его влияние на развитие некоторых злокачественных опухолей. Инфекция и иммунитет 2020;10(2):347–58. DOI: 10.15789/2220-7619-EBV-1162Smirnova K.V., Senyuta N.B., Botezatu I.V. et al. Epstein–Barr virus in the ethnic Tatars population: the infection and sequence variants of LMP1 oncogene. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2018;5(3):65–74. (In Russ.). DOI: 10.17650/2313-805X-2018-5-3-65-74Смирнова К.В., Сенюта Н.Б., Ботезату И.В. и др. Вирус Эпштейна–Барр у этнических татар: инфицированность и сиквенсные варианты онкогена LMP1. Успехи молекулярной онкологии 2018;5(3):65–74. DOI: 10.17650/2313-805X-2018-5-3-65-74Jen K.Y., Cheng J., Li J. et al. Mutational events in LMP1 gene of Epstein–Barr virus in salivary gland lymphoepithelial carcinomas. Int J Cancer 2003;105(5):654–60. DOI: 10.1002/ijc.11100Hu L.F., Zabarovsky E.R., Chen F. et al. Isolation and sequencing of the Epstein–Barr virus BNLF-1 gene (LMP1) from a Chinese nasopharyngeal carcinoma. J Gen Virol 1991;72(10):2399–409. DOI: 10.1099/0022-1317-72-10-2399Su Z.Y., Siak P.Y., Leong C.O. et al. The role of Epstein–Barr virus in nasopharyngeal carcinoma. Front Microbiol 2023;14:1116143. DOI: 10.3389/fmicb.2023.1116143Hadhri-Guiga B., Khabir A.M., Mokdad-Gargouri R. et al. Various 30 and 69 bp deletion variants of the Epstein–Barr virus LMP1 may arise by homologous recombination in nasopharyngeal carcinoma of Tunisian patients. Virus Res 2006;115(1):24–30. DOI: 10.1016/j.virusres.2005.07.002Dardari R., Khyatti M., Cordeiro P. et al. High frequency of latent membrane protein-1 30-bp deletion variant with specific single mutations in Epstein–Barr virus-associated nasopharyngeal carcinoma in Moroccan patients. Int J Cancer 2006;118 (8):1977–83. DOI: 10.1073/pnas.81.23.7632Popkova M.I., Utkin O.V. Features of the current epidemic process of infectious mononucleosis in the Nizhny Novgorod Region. Zdorov’e naseleniya i sreda obitaniya = Public Health and Habitat 2021;4(337):79–86. (In Russ.). DOI: 10.35627/22195238/202133747986Попкова М.И., Уткин О.В. Особенности эпидемического процесса инфекционного мононуклеоза в Нижегородской области в современный период. Здоровье населения и среда обитания 2021;4(337):79–86. DOI: 10.35627/22195238/202133747986Corvalan A., Ding S., Koriyama C. et al. Association of a distinctive strain of Epstein–Barr virus with gastric cancer. Int J Cancer 2006;118(7):1736–42. DOI: 10.1002/ijc.21530Corvalán A.H., Ruedlinger J., de Mayo T. et al. The phylogeographic diversity of EBV and admixed ancestry in the americas another model of disrupted human-pathogen co-evolution. Cancers (Basel) 2019;11(2):217. DOI: 10.3390/cancers11020217Lung M.L., Chang R.S., Huang M.L. et al. Epstein–Barr virus genotypes associated with nasopharyngeal carcinoma in southern China. Virology 1990;177(1):44–53. DOI: 10.1016/0042-6822(90)90458-4Ordonez P., Koriyama C., Ding S. et al. Identification of the distinctive type i/XhoI+ strain of Epstein–Barr virus in gastric carcinoma in Peru. Anticancer Res 2011;31(10):3607–13.Lee A.W.M., Lee V.H.F., Ng W.T. et al. A systematic review and recommendations on the use of plasma EBV DNA for nasopharyngeal carcinoma. Eur J Cancer 2021;153:109–22. DOI: 10.1016/j.ejca.2021.05.022Chen W.J., Xu W.N., Wang H.Y. et al. Plasma Epstein–Barr virus DNA and risk of nasopharyngeal carcinoma in a prospective seropositive population. BMC Cancer 2021;21(1):651. DOI: 10.1186/s12885-021-08408-0Smirnova K.V., Senuta N.B., Botezatu I.V. et al. Markers of Epstein–Barr virus in clinical assessment of Russian patients with nasopharyngeal cancer. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2021;8(3):14–24. (In Russ.). DOI: 10.17650/2313-805X-2021-8-3-14-24Смирнова К.В., Сенюта Н.Б., Ботезату И.В. и др. Маркеры вируса Эпштейна–Барр в оценке клинического состояния российских больных раком носоглотки. Успехи молекулярной онкологии 2021;8(3):14–24. DOI: 10.17650/2313-805X-2021-8-3-14-24Vasilyeva A.S., Molchanov A.D. Molecular markers and development of methods for early diagnosis of EBV-associated gastric cancer. Voprosy oncologii = Issues of Oncology 2023;69(3S):482–3. (In Russ.).Васильева А.С., Молчанов А.Д. Молекулярные маркеры и разработка методов ранней диагностики ВЭБ-ассоциированного рака желудка. Вопросы онкологии 2023;69(3S):482–3.Heslop H.E., Slobod K.S., Pule M.A. et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 2010;115(5):925–35. DOI: 10.1182/blood-2009-08-239186Cui X., Snapper C.M. Epstein Barr Virus: Development of vaccines and immune cell therapy for EBV-associated diseases. Front Immunol 2021;12:734471. DOI: 10.3389/fimmu.2021.734471Colby B.M., Shaw J.E., Elion G.B. et al. Effect of acyclovir 9-(2-hydroxyethoxymethyl)guanine on Epstein–Barr virus DNA replication. J Virol 1980;34(2):560–8. DOI: 10.1128/jvi.34.2.560-568.1980De Clercq E. Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF). Biochem Pharmacol 2016;119:1–7. DOI: 10.1016/j.bcp.2016.04.015Yoshizaki T., Wakisaka N., Kondo S. et al. Treatment of locally recurrent Epstein–Barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir. J Med Virol 2008;80(5):879–82. DOI: 10.1002/jmv.21165Afshar K., Rao A.P., Patel V. et al. Use of foscarnet therapy for EBV infection following control of PTLD with enhancement of cellular immunity in a lung-transplant recipient. J Transplant 2011;2011:919651. DOI: 10.1155/2011/919651Cohen J.I. Vaccine development for Epstein–Barr virus. Adv Exp Med Biol 2018;1045:477–93. DOI: 10.1007/978-981-10-7230-7_22Bu W., Joyce M.G., Nguyen H. et al. Immunization with components of the viral fusion apparatus elicits antibodies that neutralize Epstein–Barr virus in b cells and epithelial cells. Immunity 2019;50(50):1305–16e6. DOI: 10.1016/j.immuni.2019.03.010Taylor G.S., Jia H., Harrington K. et al. A recombinant modified vaccinia ankara vaccine encoding Epstein–Barr virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. Clin Cancer Res 2014;20(19):5009–22. DOI: 10.1158/1078-0432.CCR-14-1122-TSmith C., Tsang J., Beagley L. et al. Effective treatment of metastatic forms of Epstein–Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Cancer Res 2012;72(5):1116–25. DOI: 10.1158/0008-5472.CAN-11-3399Van Zyl D.G., Tsai M.H., Shumilov A. et al. Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. PLoS Pathog 2018;14(12):e1007464. DOI: 10.1371/journal.ppat.1007464Chakravorty S., Yan B., Wang C. et al. Integrated pan-cancer map of EBV-associated neoplasms reveals functional host-virus interactions. Cancer Res 2019;79(23):6010–23. DOI: 10.1158/0008-5472.CAN-19-0615Xu M., Yao Y., Chen H. et al. Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma. Nat Genet 2019;51(7):1131–6. DOI: 10.1038/s41588-019-0436-5SoRelle E.D., Dai J., Reinoso-Vizcaino N.M. et al. Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein–Barr virus infection. Cell Rep;40(9):111286. DOI: 10.1016/j.celrep.2022.111286