Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press78210.17650/2313-805X-2025-12-2-22-34REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИEpstein–Barr virus and mechanisms of molecular carcinogenesisВирус Эпштейна–Барр и механизмы молекулярного канцерогенезаhttps://orcid.org/0000-0001-5229-2285MolchanovA. D.МолчановА. Д.
Russian Federation

Artem Dmitrievich Molchanov

24 Kashirskoe Shosse, Moscow 115522

Bld. 2, 8 Trubetskaya St., Moscow 119991

Артем Дмитриевич Молчанов

115522 Москва, Каширское шоссе, 24

119991 Москва, ул. Трубецкая, 8, стр. 2

m.artem.aug@gmail.comhttps://orcid.org/0009-0004-0249-4574VasilyevaA. S.ВасильеваА. С.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-6209-977XSmirnovaK. V.СмирноваК. В.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-2835-5992NemtsovaM. V.НемцоваМ. В.
Russian Federation

Bld. 2, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

N.N. Blokhin National Medical Research Center of OncologyФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииSechenov University, Ministry of Health of RussiaФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России (Сеченовский Университет)1505202512222342706202527062025Copyright ©; 2025, Molchanov A.D., Vasilyeva A.S., Smirnova K.V., Nemtsova M.V.Copyright ©; 2025, Молчанов А.Д., Васильева А.С., Смирнова К.В., Немцова М.В.2025Molchanov A.D., Vasilyeva A.S., Smirnova K.V., Nemtsova M.V.Молчанов А.Д., Васильева А.С., Смирнова К.В., Немцова М.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/782

Epstein–Barr virus (EBV) is widespread among the human population and underlies development of numerous malignant neoplasms. The mechanism of EBV-associated carcinogenesis is based on the ability of viral proteins and microRNAs to cause genetic and epigenetic changes which can directly or indirectly stimulate cell growth, inhibit apoptosis, and protect tumor cells from the effects of their microenvironment and the host’s immune response. EBV can lead to development of such malignant neoplasms as Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal, gastric cancer, etc. The review discusses molecular mechanisms of EBV-associated carcinogenesis promoting the virus’s survival in the host’s cells, and regulating oncoproteins.

The results of more than 500 studies from the PubMed, Google Scholar, ResearchGate, Web of Science, RSCI (Russian Science Citation Index) and CyberLeninka databases performed primarily in the last 10 years were analyzed. Literature analysis has shown that EBV has a wide variety of mechanisms to avoid immune surveillance which ensures its lifelong persistence in the human body. Expression of latent proteins (in particular, EBNA1, LMP1, and LMP2A) which modulate the host’s signaling pathways, suppress apoptosis, and alter the immune response, plays the key role in its survival. Additionally, it was established that the type of latency maintained in the infected cells affects the probability of malignant transformation. For example, type II latency is characteristic of the majority of epithelial tumors, while type III is associated with lymphomas. Transition from latent to lytic phase is accompanied by expression of proteins promoting carcinogenesis. In the literature, special attention is paid to the roles of LMP1 and LMP2A oncoproteins which activate PI3K/AKT and JAK/STAT pathways disturbing regulation of cell proliferation and apoptosis. EBV-induced tumors are often characterized by epigenetic changes supporting persistence of the virus and tumor cell growth.

Therefore, EBV is capable of extorting multifactorial effects on the host cell which makes it an important subject of cancer virology. This confirms the necessity of further studies for refinement of molecular mechanisms of carcinogenesis and development of targeted therapeutic approaches to treatment of EBV-associated tumors.

Вирус Эпштейна–Барр (ВЭБ) широко распространен среди населения планеты и обусловливает возникновение многих злокачественных новообразований человека. Механизм ВЭБ-ассоциированного канцерогенеза заключается в способности вирусных белков и микроРНк вызывать генетические и эпигенетические изменения, которые могут прямо или косвенно стимулировать клеточный рост, ингибируя апоптоз или защищая опухолевые клетки от влияния, оказываемого на них микроокружением и иммунным ответом хозяина, приводить к развитию таких злокачественных новообразований, как лимфома Беркитта, лимфома Ходжкина, рак носоглотки, желудка и др. В обзоре рассмотрены молекулярные механизмы канцерогенеза, ассоциированного с ВЭБ, способствующие выживанию этого вируса в клетках хозяина и регулирующие онкобелки. проанализированы результаты более 500 исследований, проведенных преимущественно в последние 10 лет, из баз данных PubMed, Google Scholar, ResearchGate, Web of Science, РиНЦ (Российский индекс научного цитирования) и CyberLeninka.

Анализ научной литературы показал, что ВЭБ обладает большим арсеналом механизмов для уклонения от иммунного надзора, что обеспечивает его пожизненную персистенцию в организме человека. ключевую роль в этом играет экспрессия латентных белков (в частности, EBNA1, LMP1 и LMP2A), которые модулируют сигнальные пути клеток хозяина, подавляют апоптоз и изменяют иммунный ответ. Также установлено, что тип латентности, поддерживаемый в инфицированных клетках, влияет на вероятность злокачественной трансформации. Например, латентность II типа характерна для большинства эпителиальных опухолей, тогда как латентность III типа ассоциирована с лимфомами. переход из латентной в литическую фазу сопровождается экспрессией белков, способствующих онкогенезу. Особое внимание в литературе уделяется роли онкопротеинов LMP1 и LMP2A, которые активируют PI3K/AKT и JAK/STAT пути, нарушая регуляцию клеточной пролиферации и апоптоза. ВЭБ-индуцированные опухоли часто характеризуются эпигенетическими изменениями, поддерживающими вирусную персистенцию и рост опухолевых клеток. Таким образом, ВЭБ способен оказывать мультифакторное влияние на клетку-хозяина, что делает его важным объектом изучения в онковирусологии. Это подтверждает необходимость дальнейших исследований для уточнения молекулярных механизмов канцерогенеза и разработки таргетных терапевтических подходов к лечению ВЭБ-ассо циированных опухолей.

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