Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1811310.15789/2220-7619-IHO-18113REVIEWSОБЗОРЫUnknownInfectious hypothesis of multiple sclerosis and the role of HHV6A/B as one of the disease factors: epidemiological analysisИнфекционная гипотеза рассеянного склероза и роль ВГЧ6А/В как одного из факторов заболевания: эпидемиологический анализhttps://orcid.org/0000-0002-6683-71911986-8147FilatovaElena NikolaevnaФилатоваЕлена Николаевна
Russian Federation

Candidate of Sciences in Biology, leading researcher

ведущий научный сотрудник лаборатории молекулярной биологии и биотехнологии, кандидат биологических наук

el.filatova83@mail.ruhttps://orcid.org/0000-0002-7571-525X1174-6500UtkinOleg V.УткинОлег Владимирович
Russian Federation

PhD (Biology), Head of Laboratory of Molecular Biology and Biotechnology

кандидат биологических наук, заведующий лабораторией молекулярной биологии и биотехнологии

utkino2004@mail.ruhttps://orcid.org/0000-0003-3965-20338457-3501SakharnovNikolai A.СахарновНиколай Александрович
Russian Federation

PhD (Biology), Senior Researcher of Laboratory of Molecular Biology and Biotechnology

кандидат биологических наук, старший научный сотрудник лаборатории молекулярной биологии и биотехнологии

sakharnov_n@mail.ruhttps://orcid.org/0000-0003-0169-39561051-9769KhrulevAlexey vgenievichХрулевАлексей Евгеньевич
Russian Federation

Doctor of Science in Medical Sciences, associate professor, professor of Department of nervous Diseases

доктор медицинских наук, доцент, профессор кафедры нервных болезней

alexey_khrulev@mail.ruhttps://orcid.org/0000-0001-5370-40264123-6552ZaitsevaNatalia NikolaevnaЗайцеваНаталья Николаевна
Russian Federation

Doctor of Science in Medical Sciences, professor, director

Доктор медицинских наук, профессор, директор

nniiem@yandex.ruBlokhina Scientific Research Institute of Epidemiology and Microbiology of Nizhny NovgorodФБУН «Нижегородский научно-исследовательский институт эпидемиологии и микробиологии им. академика И.Н. Блохиной» РоспотребнадзораNervous Diseases of Privolzhsky Research Medical UniversityФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава России050920261201202601092026Copyright ©; , Filatova E.N., Utkin O.V., Sakharnov N.A., Khrulev A.v., Zaitseva N.N.Copyright ©; , Филатова Е.Н., Уткин О.В., Сахарнов Н.А., Хрулев А.Е., Зайцева Н.Н.Filatova E.N., Utkin O.V., Sakharnov N.A., Khrulev A.v., Zaitseva N.N.Филатова Е.Н., Уткин О.В., Сахарнов Н.А., Хрулев А.Е., Зайцева Н.Н.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/18113

In the present study, we analyzed epidemiological evidence suggesting a possible infectious nature of multiple sclerosis. Within the framework of the infectious theory, we considered potential determinants of the latitude gradient of multiple sclerosis (increase in the incidence and/or prevalence of disease with increasing distance from the equator), including differences in the intensity of circul

В настоящей работе проанализированы эпидемиологические свидетельства, указывающие на возможную инфекционную природу рассеянного склероза. В контексте инфекционной теории рассмотрены возможные причины формирования широтного градиента рассеянного склероза (роста заболеваемости и/или распространенности болезни среди населения по мере удаления от экватора), в частности, различия в интенсивности циркуляции распространенных патогенов и возрасте первичного инфицирования, различия сезонности вирусных инфекций. Рассмотрено влияние генетических и широтно-зависимых факторов (инсоляции) как модификаторов противовирусного иммунного ответа. Проанализированы результаты исследований влияния миграции на риск возникновения рассеянного склероза, согласующиеся с гипотезой наличия критического «окна» восприимчивости к болезни в детском и подростковом возрасте. Особое внимание уделено изучению ассоциации заболевания с предполагаемыми этиологическими агентами — вирусом герпеса человека 6А (ВГЧ6А) и вирусом герпеса человека 6В (ВГЧ6В), а также оценке их потенциальной роли в патогенезе рассеянного склероза. Повсеместная распространенность двух вирусов, первичное инфицирование в детском и подростковом возрасте и формирование пожизненной латентной инфекции с эпизодами реактивации позволяют предложить ВГЧ6А и ВГЧ6В на роль кофакторов рассеянного склероза в инфекционной модели развития заболевания. Способность двух вирусов поражать клетки иммунной системы и нервной ткани (включая глиальные клетки), способствовать развитию хронического нейровоспаления и процессов демиелинизации определяет механизм их возможного патогенетического действия. Поскольку ВГЧ6А рассматривается как более нейротропный вид вируса, а ВГЧ6В отличается высокой распространенностью и более ранним инфицированием, в работе приведено сопоставление экспериментальных данных о потенциальной роли двух вирусов в развитии рассеянного склероза. Отдельно рассмотрен вопрос влияния молекулярно-генетического полиморфизма ВГЧ6А и ВГЧ6В на их способность модулировать характер иммунного ответа на инфекцию и тем самым влиять на риск развития заболевания. В работе представлены результаты собственных эпидемиологических исследований авторов. Сделано предположение о наличии связи частот встречаемости различных геновариантов ВГЧ6А и ВГЧ6В с заболеваемостью рассеянным склерозом в популяции некоторых стран, в том числе стран Северной Европы и Северной Америки, характеризующихся аномально высокой распространенность заболевания. На примере Нижегородской области проведено сравнение многолетних циклов заболеваемости рассеянным склерозом и частот встречаемости геновариантов ВГЧ6В в европейской части России.

multiple sclerosisMSepidemiologylatitude gradientinfectious hypothesisHHV6AHHV6Bgenovariantsmolecular genetic polymorphismtime series.рассеянный склерозРСэпидемиологияширотный градиентинфекционная гипотезаВГЧ6АВГЧ6Вгеновариантымолекулярно-генетический полиморфизмвременные ряды.Отраслевая научно-исследовательская программа 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»Rospotrebnadzor's Sectoral Research Program for 2026–2030: "Scientific Support for Epidemiological Management of Socially Significant, Particularly Dangerous Infections and State Biosecurity Based on Genomic Epidemiological Surveillance, Synthetic Biology, and Digital Technologies"п. 1.3.4

In the present study, we analyzed epidemiological evidence suggesting a possible infectious nature of multiple sclerosis. Within the framework of the infectious theory, we considered potential determinants of the latitude gradient of multiple sclerosis (increase in the incidence and/or prevalence of disease with increasing distance from the equator), including differences in the intensity of circulation of common pathogens, age of primary infection, differences in the seasonality of viral infections. We also examined the contribution of genetic and latitude-related factors (insolation) as modifiers of antiviral immune responses. Studies of migration impact upon the risk of multiple sclerosis were analyzed and found to be consistent with the hypothesis of a critical “window” of susceptibility to the disease during childhood and adolescence. Particular attention was given to the association of multiple sclerosis with putative etiological agents – human herpesvirus 6A (HHV6A) and human herpesvirus 6B (HHV6B) – and their potential role in pathogenesis of multiple sclerosis. Within an infectious model of disease development, ubiquitous distribution of both viruses, primary infection in childhood and adolescence, establishment of lifelong latent infection with reactivation episodes support the proposition that HHV6A and HHV6B may act as cofactors of multiple sclerosis. Ability of viruses to infect cells of the immune system and the nervous tissue (including glial cells), to promote chronic neuroinflammation and to contribute to demyelinating processes provides a plausible mechanism of their potential pathogenic effects. HHV6A is considered to be more neurotropic, while HHV6B has higher prevalence and earlier primary infection, so we compared experimental evidence regarding the potential roles of two viruses in multiple sclerosis development. We additionally addressed how molecular genetic polymorphism of HHV6A and HHV6B may modulate the nature of immune responses to infection and thereby influence the risk of disease. We also propose a potential association between the population frequencies of distinct HHV6A and HHV6B genovariants and multiple sclerosis incidence in certain countries of Northern European and North American with unusually high disease prevalence. Using Nizhny Novgorod Region as a case study, we compared long-term cycles of multiple sclerosis incidence with frequencies of HHV6B genovariants in the European part of Russia.

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