Вопросы вирусологии. 2020; 65: 191-202
Вирус Эпштейна-Барр (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4): репликативные стратегии
https://doi.org/10.36233/0507-4088-2020-65-4-191-202Аннотация
Вирус Эпштейна-Барр (ВЭБ) - один из наиболее распространённых в человеческой популяции, он способен на протяжении всей жизни персистировать в покоящихся В-клетках памяти, в Т-клетках (ВЭБ 2-го типа) и в некоторых недифференцированных эпителиальных клетках. У большинства людей персистенция ВЭБ не сопровождается значительными симптомами, но при частых активациях вируса возрастают риски тяжёлых сопутствующих заболеваний, включая хроническую активную ВЭБ-инфекцию, гемофагоцитарный лимфогистиоцитоз, рассеянный склероз, системную красную волчанку, карциному желудка и носоглотки, а также различные Т- и В-клеточные лимфомы. Большой интерес представляют молекулярные вирусные и клеточные процессы во время бессимптомной или малосимптомной персистенции ВЭБ. В этом обзоре рассматриваются поведение вирусной ДНК в заражённой клетке, формы её существования (линейная, циркулярная эписома, хромосомно-интегрированная форма), а также методы копирования генома ВЭБ. Рассмотрены два тесно связанных цикла вируса - литический и латентный. Литическая активация неблагоприятна для выживания конкретного вирусного генома в клетке, она запускается в результате дифференцировки латентно инфицированной клетки или появления стресс-сигналов из-за неблагоприятных условий внеклеточной среды. ВЭБ обладает большим количеством адаптивных механизмов для предотвращения литической реактивации и снижения враждебности иммунных клеток хозяина. Понимание молекулярных аспектов персистенции ВЭБ поможет в будущем разработать более эффективные, таргетные препараты для лечения как самой вирусной инфекции, так и сопутствующих заболеваний.
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Problems of Virology. 2020; 65: 191-202
Epstein-Barr virus (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4): replication strategies
https://doi.org/10.36233/0507-4088-2020-65-4-191-202Abstract
The Epstein-Barr virus (EBV), one of the most common in the human population, is capable of lifelong persistence in resting memory B-cells, in T-cells in case of type 2 EBV, and in some undifferentiated epithelial cells. In most people, EBV persistence is not accompanied by significant symptoms, but frequent virus activations are associated with the increased risks of severe diseases, such as chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis, multiple sclerosis, systemic lupus erythematosus, gastric and nasopharyngeal carcinomas, and a variety of T- and B-cell lymphomas. Therefore, the molecular viral and host cell processes during asymptomatic or low-symptom EBV persistence are of great interest. This review describes the behavior of the viral DNA in an infected cell and the forms of its existence (linear, circular episome, chromosomally integrated forms), as well as methods of EBV genome copying. Two closely related cycles of viral reproduction are considered. Lytic activation is unfavorable for the survival of a particular viral genome in the cell, and may be a result of differentiation of a latently infected cell, or the arrival of stress signals due to adverse extracellular conditions. The EBV has a large number of adaptive mechanisms for limiting lytic reactivation and reducing hostility of host immune cells. Understanding the molecular aspects of EBV persistence will help in the future develop more effective targeted drugs for the treatment of both viral infection and associated diseases.
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