Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC86610.15690/vramn866INFECTIOUS DISEASES: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ИНФЕКЦИОННЫХ БОЛЕЗНЕЙTHE MECHANISMS OF IMMUNE ESCAPE BY HEPATITIS B VIRUSМЕХАНИЗМЫ ИММУНОЛОГИЧЕСКОГО УСКОЛЬЗАНИЯ ВИРУСА ГЕПАТИТА Вhttps://orcid.org/0000-0002-2836-8232SokolovaM. V.СоколоваМарина Владимировна
Russian Federation

Moscow

Аспирант, младший научный сотрудник лаборатории медиаторов и эффекторов иммунитета отдела иммунологиию

123098, Москва, ул. Гамалеи, д. 18, тел.: +7 (499) 193-61-31, SPIN-код: 8100-0056

sokolova_mariya_gamaleya@mail.ruhttps://orcid.org/0000-0002-9724-695XKonoplevaM. V.КоноплеваМария Вениаминовна
Russian Federation

Moscow

Кандидат биологических наук, старший научный сотрудник лаборатории медиаторов и эффекторов иммунитета отдела иммунологии.

123098, Москва, ул. Гамалеи, д. 18, тел.: +7 (499) 193-61-31, SPIN-код: 9680-6301

maria-konopleva@rambler.ruhttps://orcid.org/0000-0002-6686-9011SemenenkoТ. A.СемененкоТатьяна Анатольевна

Moscow

Доктор медицинских наук, профессор, главный научный сотрудник, руководитель лаборатории неспецифической профилактики инфекционных заболеваний, руководитель отдела эпидемиологии.

123098, Москва, ул. Гамалеи, д. 18, тел.: +7 (499) 190-72-56, SPIN-код: 8375-2270

semenenko@gamaleya.orghttps://orcid.org/0000-0001-8139-0247AkimkinV. G.АкимкинВасилий Геннадьевич
Russian Federation

Moscow

Доктор медицинских наук, профессор, академик РАН, заместитель директора по эпидемиологии.

111123, Москва, ул. Новогиреевская, д. 3а, тел.: +7 (495) 672-10-69, SPIN-код: 4038-7455

vgakimkin@yandex.ruhttps://orcid.org/0000-0002-2706-6689TutelyanA. V.ТутельянАлексей Викторович
Russian Federation

Moscow

Доктор медицинских наук, профессор, член-корреспондент РАН, заведующий лабораторией инфекций, связанных с оказанием медицинской помощи.

111123, Москва, ул. Новогиреевская, д. 3а, тел.: +7 (495) 672-10-69, SPIN-код: 8150-2230

willothewisp@yandex.ruhttps://orcid.org/0000-0001-5731-3284SuslovA. P.СусловАнатолий Петрович
Russian Federation

Moscow

Доктор медицинских наук, профессор, ведущий научный сотрудник, руководитель лаборатории медиаторов и эффекторов иммунитета отдела иммунологии.

123098, Москва, ул. Гамалеи, д. 18, тел.: +7 (499) 193-61-31, eLibrary Author ID: 251813suslov.anatoly@gmail.comN.F. Gamaleya Federal Research Centre of Epidemiology and MicrobiologyНациональный исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф. ГамалеиCentral Research Institute of EpidemiologyЦентральный научно-исследовательский институт эпидемиологии Роспотребнадзора231220177264084190407201722112017Copyright ©; 2017, "Paediatrician" Publishers LLCCopyright ©; 2017, Издательство "Педиатръ"2017"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/article/view/866

The high prevalence of the hepatitis B virus (HBV) in population occurs mainly due to numerous mechanisms formed in the process of the virus evolution, contributing to its survival under immunological pressure. The review presents the most complete systematization and classification of various HBV protective mechanisms basing on their influence on different parts of congenital and adaptive immune response. The analysis of literature data allows for the conclusion that two basic principles underlie the mechanisms: the strategy of the «stealth virus» (virus’s escape from recognition by the immune system) and strategy of immunosuppression. The stealth virus strategy is performed as follows: special strategy of the HBV replication which prevents the recognition by the receptors of congenital immune system; occurrence of the vaccine escape mutants; isolation of the virus in host cells and tissues providing its inaccessibility to T-cells along with hyperproduction of subviral particles as traps for specific antibodies. The core principle of the immunosuppression implemented in hepatitis B therapy is based on the phenomenon of the viral apoptotic mimicry. The result of this interaction strategy is dysfunction of NK and NKT-cells, inactivation of dendritic cell functions, and suppression of the adaptive immune response. The review demonstrates that interaction between HBV and the immune system of the macro organism is in some kind of «dynamic equilibrium» depending on numerous factors. Specific molecular targets of the viral impact are described. We propose to expand the research on the influence of the host’s genetic factors on the development of congenital and adaptive immune response against HBV, especially during the real infectious process which results in the improvement of approaches to the therapy by developing personalized treatment methods.

Высокая распространенность вируса гепатита В (HBV) среди населения во многом обусловлена многочисленными механизмами, сформированными в ходе эволюции этого вируса, способствующими его выживанию в условиях иммунологического прессинга. В обзоре представлены наиболее полная систематизация и классификация разнообразных защитных механизмов HBV с точки зрения их воздействия на различные звенья врожденного и адаптивного иммунного ответа. Анализ литературных данных позволяет сделать заключение, что в основе всех этих механизмов заложено два базовых принципа ― стратегия «вируса-невидимки» (уход вируса от распознавания иммунной системой) и стратегия иммуносупрессии. Тип взаимодействия вируса с иммунной системой, называемый стратегией «вируса-невидимки», осуществляется следующими способами: особая стратегия репликации HBV, препятствующая распознаванию рецепторами системы врожденного иммунитета, — появление мутантов вакцинального ускользания; изоляция вируса в клетках и тканях организма-хозяина, обеспечивающая его недоступность для Т-клеток, а также гиперпродукция субвирусных частиц в качестве ловушек для специфичных антител. Базовый принцип стратегии иммуносупрессии, реализуемый в случае HBV, основан, по мнению авторов, преимущественно на явлении вирусной апоптотической мимикрии. Результатом данной стратегии взаимодействия являются дисфункция NK- и NKT-клеток, инактивация функций дендритных клеток и угнетение системы адаптивного иммунного ответа. В обзоре показано, что взаимодействие между HBV и иммунной системой макроорганизма находится в некоем «динамическом равновесии», зависящем от разнообразных факторов. Описаны конкретные молекулярные мишени вирусного воздействия. Предлагается расширить исследования о влиянии генетических факторов хозяина на развитие врожденного и адаптивного иммунного ответа против HBV, особенно при изучении реального инфекционного процесса, что позволит усовершенствовать подходы к терапии гепатита В в направлении разработки методов персонализированной медицины.

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