Вирус Эпштейна–Барр и механизмы молекулярного канцерогенеза

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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