Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI172910.15789/2220-7619-MGA-1729REVIEWSОБЗОРЫMolecular genetic and clinical aspects of socially relevant viruses underlying congenital diseasesМолекулярно-генетические и клинические аспекты социально значимых вирусов в реализации врожденных заболеванийhttps://orcid.org/0000-0002-7336-8805VasilevV. V.ВасильевВ. В.
Russian Federation

Valerii V. Vasilev,  PhD, MD (Medicine), Professor, Head of the Research Department of Congenital Infectious Diseases; Professor, Department of Infectious Diseases

191015, St. Petersburg, Professor Popov str., 9

Phone: +7 (812) 234-60-04 (office), +7 921 940-93-84 (mobile)

Fax: +7 (812) 234-96-91 

Васильев Валерий Викторович,  д.м.н., профессор, зав. научно-исследовательским отделом врожденных инфекционных заболеваний; профессор кафедры инфекционных болезней 

191015, Cанкт-Петербург, ул. Профессора Попова, 9

Тел.: 8 (812) 234-60-04 (служебн.), 8 921 940-93-84 (моб.),

Факс: 8 (812) 234-96-91

vcubed@ya.ruhttps://orcid.org/0000-0003-0968-6291RogozinaN. V.РогозинаН. В.
Russian Federation

PhD (Medicine), Senior Researcher, Department of Congenital Infectious Diseases; Associate Professor, Department of Infectious Diseases in Children

St. Petersburg 

к.м.н., старший научный сотрудник научно-исследовательского отдела врожденных инфекционных заболеваний; доцент кафедры инфекционных заболеваний у детей ФП и ДПО 

Санкт-Петербург 

lelekin96@mail.ruhttps://orcid.org/0000-0002-5796-5896GrinevaA. A.ГриневаА. А.
Russian Federation

PhD (Medicine), Researcher, Department of Congenital Infectious Diseases

St. Petersburg 

к.м.н., научный сотрудник научно-исследовательского отдела врожденных инфекционных заболеваний 

a.a.grineva@gmail.comPediatric Research and Clinical Center for Infectious DiseasesФГБУ Детский научно-клинический центр инфекционных болезней ФМБА РоссииNorth-Western State Medical University named after I.I. MechnikovФГБОУ ВО Северо-Западный государственный медицинский университет им. И.И. МечниковаSt. Petersburg State Pediatric Medical UniversityФГБОУ ВО Санкт-Петербургский государственный педиатрический медицинский университет Минздрава России200920211146356482904202130052021Copyright ©; 2021, Vasilev V.V., Rogozina N.V., Grineva A.A.Copyright ©; 2021, Васильев В.В., Рогозина Н.В., Гринева А.А.2021Vasilev V.V., Rogozina N.V., Grineva A.A.Васильев В.В., Рогозина Н.В., Гринева А.А.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/1729

Congenital viral infectious diseases are characterized by polyetiologic pathology holding an important place in the structure of perinatal losses. Due to the wide distribution and lack of specific prophylaxis, the problem of herpesvirus infections is of greatest interest, namely of herpes infection caused by herpes simplex virus type 1 and 2, human herpes simplex virus type 6 and cytomegalovirus infection, as well as parvovirus infection B19. The opportunities to investigate a relation between manifestations of the infectious process and host molecular genetic characteristics have been expanded after developing full genome sequencing methods and creating genetic data international banks. It has been proven that herpes virus genetic variations can account for related neurovirulence, showing that diverse cytomegalovirus genotypes are associated with hepatosplenomegaly, hearing impairment and the symptoms of the central nervous system diseases. Nevertheless, the data on correlation between genotypes and clinical manifestations are still scarce and contradictory, whereas high level of variability becomes extremely evident while comparing genomic sequences of viral strains. The herpesvirus type 6 has been proven to integrate into germ cells with potential for subsequent vertical transmission of chromosomally integrated virus to the offspring and its further intergeneration inheritance. А direct relationship between B19V genospecies and disease manifestations including congenital infections has not yet been identified. Taking into account possible differences in the geographical distribution of such viruses on the territory of the Russian Federation, ethnic populational characteristics, and high frequency of related congenital infectious diseases with a wide range of clinical manifestations, it seems promising to expand scientific research on the genotyping of herpes simplex viruses, cytomegalovirus, herpes viruses type 6 and parvovirus B19V in Russia. The results of such studies will be demanded by practical healthcare in order to develop and use more effective etiotropic drugs and specific prophylaxis in the light of trends to develop personalized and preventive medicine.

Врожденные вирусные инфекционные заболевания — полиэтиологичная патология, занимающая важное место в структуре перинатальных потерь. Ввиду их широкого распространения и отсутствия специфической профилактики наибольший интерес представляет проблема герпесвирусных инфекций, а именно герпетической инфекции, вызванной вирусом простого герпеса 1 и 2 типа, герпесвирусной инфекции, вызванной вирусом герпеса человека 6 типа, и цитомегаловирусной инфекции, а также парвовирусной инфекции В19. С развитием методов полногеномного секвенирования и созданием международных банков генетических данных расширились возможности изучения зависимости проявлений инфекционного процесса от молекулярно-генетических характеристик микроорганизмов. Доказано, что генетические вариации герпесвирусов могут определять их нейровирулентность, а различные генотипы цитомегаловируса ассоциированы с гепатоспленомегалией, нарушением слуха и симптомами заболеваний центральной нервной системы. Тем не менее данные о корреляции между генотипами и клиническими проявлениями все еще фрагментарны и противоречивы, а при сравнении геномных последовательностей штаммов становится очевидным чрезвычайно высокий уровень их вариабельности. Для вируса герпеса 6 типа доказана интеграция вируса в герминативные клетки с возможностью последующей вертикальной передачи хромосомно-интегрированного вируса потомству и дальнейшего его наследования от поколения к поколению. Прямая связь между различными геновидами парвовируса B19V и клиническими проявлениями заболевания, в том числе врожденного, до настоящего времени не установлена. Перспективным представляется расширение научного поиска по генотипированию вирусов простого герпеса, цитомегаловируса, вирусов герпеса 6 типа, парвовируса В19V в России с учетом возможных различий в географическом распространении этих вирусов на территории страны, этнических особенностей населения, высокой частоты вызываемых этими вирусами врожденных инфекционных заболеваний с широким спектром клинических проявлений. Результаты этих поисков будут востребованы практическим здравоохранением для разработки и применения более эффективных этиотропных препаратов и средств специфической профилактики с учетом тенденций развития персонифицированной и превентивной медицины.

congenital infectionsintrauterine infectionspregnancychildrennewbornsantenatal mortalityneonatal mortalityherpes simplex virus 1herpes simplex virus 2human herpes virus 6cytomegalovirusparvovirus B19врожденные инфекциивнутриутробные инфекциибеременностьдетиноворожденныеантенатальная смертностьнеонатальная смертностьвирус простого герпеса 1 типавирус простого герпеса 2 типавирус герпеса человека 6 типацитомегаловируспарвовирус В19The reported study was funded by Russian Foundation for Basic Research within research project No. 20-115-50439 “Expansion”.Статья подготовлена при финансовой поддержке гранта РФФИ по реализации научного проекта № 20-115-50439 «Экспансия».1. Антипова А.Ю., Хамитова И.В., Останкова Ю.В., Семенов А.В., Бичурина М.А., Лаврентьева И.Н. Молекулярногенетическая характеристика изолятов парвовируса B19, циркулирующих на территории Северо-Западного федерального округа // Журнал микробиологии, эпидемиологии и иммунобиологии. 2018. № 6. С. 55–61. [Antipova A.Yu., Hamitova I.V., Ostankova Yu.V., Semenov A.V., Bichurina M.A., Lavrent’eva I.N. Molecular genetic characteristics of parvovirus B19 isolates circulating in the Northwestern Federal District. Zhurnal mikrobiologii, epidemiologii i immuno biologii = Journal of Microbiology, Epidemiology and Immunobiology, 2018, no. 6, pp. 55–61. (In Russ.)] doi: 10.36233/0372-9311-2018-6-55-612. Антипова А.Ю., Лаврентьева И.Н. Вирусы семейства Parvoviridae: молекулярно-генетические аспекты репродукции и медицинская значимость // Инфекция и иммунитет. 2017. Т. 7, № 1. С. 7–20. [Antipova A.Yu., Lavrent’eva I.N. Viruses of the Parvoviridae family: molecular genetic aspects of reproduction and medical significance. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2017, vol. 7, no. 1, pp. 7–20. (In Russ.)] doi: 10.15789/2220-7619-2017-1-7-203. Володин Н.Н. Актуальные проблемы неонатологии. М.: ГЭОТАР-Мед, 2004. 448 с. [Volodin N.N. Actual problems of neonatology. Moscow: GEOTAR-Med, 2004. 448 p. (In Russ.)]4. Гринева А.А., Васильев В.В., Каштанова Т.А., Кянксеп И.В. Антенатальная диагностика и терапия врожденной инфекции, вызванной парвовирусом В19 (клинический случай) // Журнал инфектологии. 2020. Т. 12, № 4. С. 109–113. [Grineva A.A., Vasilev V.V., Kashtanova T.A., Kyanksep I.V. Antenatal diagnosis and therapy of congenital infection caused by parvovirus B19 (clinical case). Zhurnal infektologii = Journal of Infectology, 2020, vol. 12, no. 4, pp. 109–113. (In Russ.)] doi: 10.22625/2072-6732-2020-12-4-109-1135. Ермолович М.А., Семейко Г.В., Самойлович Е.О. Генетические варианты парвовируса B19, циркулирующие в Беларуси в течение эпидемического цикла инфекции (2005–2016) // Известия Национальной академии наук Беларуси. Серия медицинских наук. 2019. Т. 16, № 1. С. 35–45. [Ermolovich M.A., Semejko G.V., Samojlovich E.O. Genetic variants of parvovirus B19 circulating in Belarus during the epidemic cycle of infection (2005–2016). Izvestiia Natsional’noy akademii nauk Belarusi. Seriia meditsinskikh nauk = News of the National Academy of Sciences of Belarus. Medical Science Series, 2019, vol. 16, no. 1, pp. 35–45. (In Russ.)] doi: 10.29235/1814-6023-2019-16-1-35-456. Ермолович М.А., Семейко Г.В., Самойлович Е.О. Молекулярная эпидемиология парвовирусной инфекции в Республике Беларусь // Вопросы вирусологии. 2010. Т. 55, № 2. С. 26–31. [Ermolovich M.A., Semejko G.V., Samojlovich E.O. Molecular epidemiology of parvovirus infection in the Republic of Belarus. Voprosy virusologii = Problems of Virology, 2010, vol. 55, no. 2, pp. 26–31. (In Russ.)]7. Ермолович М.А., Семейко Г.В., Самойлович Е.О., Хрусталев В.В. Разнообразие геновариантов парвовируса В19, циркулировавших в Беларуси в 2017–2018 гг. // Медицинский журнал. 2020. № 2 (72). С. 55–60. [Ermolovich M.A., Semejko G.V., Samojlovich E.O., Hrustalev V.V. Diversity of genovariants of parvovirus B19 circulating in Belarus in 2017–2018. Meditsinskii zhurnal = Medical Journal, 2020, no. 2 (72), pp. 55–60. (In Russ.)]8. Куюмчьян С.Х., Васильев В.В., Алексеева Н.П. Факторы риска и прогноз развития некоторых актуальных врожденных (внутриутробных) инфекций // Журнал инфектологии. 2016. Т 8, № 1. С. 38–44. [Kuyumchyan S.H., Vasilev V.V., Alekseeva N.P. Risk factors and prognosis for the development of some actual congenital (intrauterine) infections. Zhurnal infektologii = Journal of Infectology, 2016, vol. 8, no. 1, pp. 38–44. (In Russ.)]9. Лаврентьева И.Н., Антипова А.Ю., Семенов А.В., Бичурина М.А. Генотипирование изолятов парвовируса В19, циркулирующих в Северо-Западном федеральном округе России // Журнал микробиологии, эпидемиологии и иммунобиологии. 2013. № 6. C. 36–43. [Lavrenteva I.N., Antipova A.U., Semenov A.V., Bichurina M.A. Genotyping of parvovirus B19 isolates circulating in the Northwestern Federal District of Russia. Zhurnal mikrobiologii, epidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology, 2013, no. 6, pp. 36–43. (In Russ.)]10. Лобзин Ю.В., Скрипченко Н.В., Васильев В.В., Рогозина Н.В., Бабаченко И.В., Левина А.С., Харит С.М., Бехтерева М.К., Рулева А.А., Сиземов А.Н., Иванова М.В., Техова И.Г., Ушакова Г.М., Осипова З.А., Голева О.В., Комарова А.М., Бухалко М.А. Диагностика, лечение и профилактика актуальных врожденных инфекций: учебное пособие для интернов, ординаторов, врачей-педиатров, врачей общей практики, инфекционистов. СПб.: СПбГПМУ, 2017. 64 с. [Lobzin Y.V., Skripchenko N.V., Vasilev V.V., Rogozina N.V., Babachenko I.V., Levina A.S., Harit S.M., Bekhtereva M.K., Ruleva A.A., Sizemov A.N., Ivanova M.V., Tekhova I.G., Ushakova G.M., Osipova Z.A., Goleva O.V., Komarova A.M., Buhalko M.A. Diagnostics, treatment and prevention of actual congenital infections: a textbook for interns, residents, pediatricians, general practitioners, infectious disease specialists. St. Petersburg: St. Petersburg State Pediatric Medical University, 2017. 64 p. (In Russ.)]11. Неонатология: национальное руководство. Под ред. Н.Н. Володина. М.: ГЭОТАР-Медиа, 2007. 896 с. [Neonatology: a national guide. Ed. by N.N. Volodin. Moscow: GEOTAR-Media, 2007. 896 p. (In Russ.)]12. Об утверждении перечня социально значимых заболеваний и перечня заболеваний, представляющих опасность для окружающих (в редакции постановлений Правительства Российской Федерации от 13.07.2012 № 710, от 31.01.2020 № 66): постановление Правительства РФ № 715 от 01.12.2004 г. [On approval of the list of socially significant diseases and the list of diseases that pose a danger to others (as amended by decrees of the Government of the Russian Federation of 13.07.2012 No. 710, of 31.01.2020 no. 66): decree of the Government of the Russian Federation No. 715 of 01.12.2004. (In Russ.)] URL: http://government.ru/docs/all/5061413. Akhtar L.N., Bowen C.D., Renner D.W., Pandey U., Della Fera A.N., Kimberlin D.W., Prichard M.N., Whitley R.J., Weitzman M.D., Szpara M.L. Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population. mSphere, 2019, vol. 4, no. 1: e00590-18. doi: 10.1128/mSphere.00590-1814. Alcami A. Viral mimicry of cytokines, chemokines and their receptors. Nat. Rev., 2003, vol. 3, no. 1, pp. 36–50. doi: 10.1038/nri98015. Alwan S.N., Shamran H.A., Ghaib A.H., Kadhim H.S., Al-Mayah Q.S., Al-Saffar A.J., Bayati A.H., Arif H.S., Fu J., Wickes B.L. Genotyping of Cytomegalovirus from symptomatic infected neonates in Iraq. AJTHAB, 2019, vol. 100, no. 4, pp. 957–963. doi: 10.4269/ajtmh.18-015216. Arav-Boger R., Willoughby R.E., Pass R.F., Zong J.C., Jang W.J., Alcendor D., Hayward G.S. Polymorphisms of the cytomegalovirus (CMV)-encoded tumor necrosis factor-alpha and beta-chemokine receptors in congenital CMV disease. J. Infect. Dis., 2002, vol. 186, no. 8, pp. 1057–1064. doi: 10.1086/34423817. Arbuckle J.H., Medveczky M.M., Luka J., Hadley S.H., Luegmayr A., Ablashi D., Lund T.C., Tolar J., De Meirleir K., Montoya J.G., Komaroff A.L., Ambros P.F., Medveczky P.G. The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc. Natl. Acad. Sci. USA, 2010, vol. 107, no. 12, pp. 5563–5568. doi: 10.1073/pnas.091358610718. Arellano-Galindo J., Villanueva-García D., Cruz-Ramirez J.L., Yalaupari-Mejìa J.P., Uribe-Gutiérrez G., VelazquezGuadarrama N., Nava-Frias M., Munoz-Hernández O., Mejía-Arangure J.M. Detection and gB genotyping of CMV in Mexican preterm infants in the context of maternal seropositivity. JIDC, 2014, vol. 8, no. 6, pp. 758–767. doi: 10.3855/jidc.350119. Attwood L.O., Holmes N.E., Hui L. Identification and management of congenital parvovirus B19 infection. Prenat. Diagn., 2020, vol. 40, no. 13, pp. 1722–1731. doi: 10.1002/pd.581920. Barlinn R., Trogstad L., Rollag H., Frøen F., Magnus P., Dudman S.G. Parvovirus B19 DNAemia in pregnant women in relation to perinatal death: a nested case-control study within a large population-based pregnancy cohort. Acta Obstet. Gynecol. Scand., 2020, vol. 99, no. 7, pp. 856–864. doi: 10.1111/aogs.1380121. Bascietto F., Liberati M., Murgano D., Buca D., Iacovelli A., Flacco M.E., Manzoli L., Familiari A., Scambia G., D’Antonio F. Outcome of fetuses with congenital parvovirus B19 infection: systematic review and meta-analysis. Ultrasound Obstet. Gynecol., 2018, vol. 52, no. 5, pp. 569–576. doi: 10.1002/uog.1909222. Belanger B.G., Lui F. Embryology, teratology TORCH. In: Treasure Island (FL). StatPearls Publishing, 2019. URL: https://www.ncbi.nlm.nih.gov/books/NBK545148/23. Bell A.J., Gallagher A., Mottram T., Lake A., Kane E.V., Lightfoot T., Roman E., Jarrett R.F. Germ-line transmitted, chromoso mally integrated HHV-6 and classical Hodgkin lymphoma. PLoS One, 2014, vol. 9, no. 11: e112642. doi: 10.1371/journal.pone.011264224. Boeckh M., Geballe A.P. Cytomegalovirus: pathogen, paradigm, and puzzle. J. Clin. Investig., 2011, vol. 121, no. 5, pp. 1673– 1680. doi: 10.1172/JCI4544925. Bowden R., Sakaoka H., Ward R., Donnelly P. Patterns of Eurasian HSV-1 molecular diversity and inferences of human migrations. Infect. Genet. Evol., 2006, vol. 6, no. 1, pp. 63–74. doi: 10.1016/j.meegid.2005.01.004.20–2226. Britt W.J. Human cytomegalovirus infection in women with preexisting immunity: sources of infection and mechanisms of infection in the presence of antiviral immunity. J. Infect. Dis., 2020, vol. 221, no. 1, pp. S1–S8. doi: 10.1093/infdis/jiz46427. Cagliani R., Forni D., Mozzi A., Sironi M. Evolution and genetic diversity of primate cytomegaloviruses. Microorganisms, 2020, vol. 8, no. 5: 624. doi: 10.3390/microorganisms805062428. Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R., Horsnell T., Hutchison C.A. 3rd, Kouzarides T., Martignetti J.A., Barrell B.G. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr. Top Microbiol. Immunol., 1990, no. 154, pp. 125–69. doi: 10.1007/978-3-642-74980-3_629. Chou S.W., Scott K.M. Rises in antibody to human herpesvirus 6 detected by enzyme immunoassay in transplant recipients with primary cytomegalovirus infection. J. Clin. Microbiol., 1990, vol. 28, no. 5, pp. 851–854. doi: 10.1128/JCM.28.5.851-854.199030. Clark D.A. Clinical and laboratory features of human herpesvirus 6 chromosomal integration. Clin. Microbiol. Infect., 2016, vol. 22, no. 4, pp. 333–339. doi: 10.1016/j.cmi.2015.12.02231. Corey L., Whitley R.J., Stone E.F., Mohan K. Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome. Lancet, 1988, vol. 331, no. 8575–8576, pp. 1–4. doi: 10.1016/s0140-6736(88)90997-x32. Cossart Y.E., Field A.M., Cant B., Widdows D. Parvovirus-like particles in human sera. Lancet, 1975, vol. 305, no. 7898, pp. 72–73. doi: 10.1016/s0140-6736(75)91074-033. Cotmore S.F., Agbandje-McKenna M., Canuti M., Chiorini J.A., Eis-Hubinger A.M., Hughes J., Mietzsch M., Modha S., Ogliastro M., Pénzes J.J., Pintel D.J., Qiu J., Soderlund-Venermo M., Tattersall P., Tijssen P.; ICTV Report Consortium. ICTV virus taxonomy profile: Parvoviridae. J. Gen. Virol., 2019, vol. 100, no. 3, pp. 367–368. doi: 10.1099/jgv.0.00121234. Craig J.M., MaCauley J.C., Weller T.H., Wirth P. Isolation of intranuclear inclusion producing agents from infants with illnesses resembling cytomegalic inclusion disease. SEBM, 1957, vol. 94, no. 1, pp. 4–12. doi: 10.3181/00379727-94-2284135. Daibata M., Taguchi T., Taguchi H., Miyoshi I. Integration of human herpesvirus 6 in a Burkitt’s lymphoma cell line. Br. J. Haematol., 1998, vol. 102, no. 5, pp. 1307–1313. doi: 10.1046/j.1365-2141.1998.00903.x36. De Vries J.J., Wessels E., Korver A.M., van der Eijk A.A., Rusman L.G., Kroes A.C., Vossen A.C. Rapid genotyping of cytomegalovirus in dried blood spots by multiplex real-time PCR assays targeting the envelope glycoprotein gB and gH genes. J. Clin. Microbiol., 2012, vol. 50, no. 2, pp. 232–237. doi: 10.1128/JCM.05253-1137. Depledge D.P., Kundu S., Jensen N.J., Gray E.R., Jones M., Steinberg S., Gershon A., Kinchington P.R., Schmid D.S., Balloux F., Nichols R.A., Breuer J. Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans. Mol. Biol. Evol., 2014, vol. 31, vol. 2., pp. 397–409. doi: 10.1093/molbev/mst210.2738. Ekman A., Hokynar K., Kakkola L., Kantola K., Hedman L., Bondén H., Gessner M., Aberham C., Norja P., Miettinen S., Hedman K., Söderlund-Venermo M. Biological and immunological relations among human parvovirus B19 genotypes 1 to 3. J. Virol., 2007, vol. 81, no. 13, pp. 6927–6935. doi: 10.1128/JVI.02713-0639. Emery V.C., Lazzarotto T. Cytomegalovirus in pregnancy and the neonate. F1000Research, 2017, vol. 6: 138. doi: 10.12688/f1000research.10276.140. Enders G., Daiminger A., Bäder U., Exler S., Enders M. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J. Clin. Virol., 2011, vol. 52, no. 3, pp. 244–246. doi: 10.1016/j.jcv.2011.07.00541. Endo A., Watanabe K., Ohye T., Suzuki K., Matsubara T., Shimizu N., Kurahashi H., Yoshikawa T., Katano H., Inoue N., Imai K., Takagi M., Morio T., Mizutani S. Molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6A in a patient with X-linked severe combined immunodeficiency. Clin. Infect. Dis., 2014, vol. 59, no. 4, pp. 545–548. doi: 10.1093/cid/ciu32342. Fernandes N.D., Arya K., Ward R. Congenital Herpes Simplex. In: Treasure Island (FL). StatPearls Publishing, 2021. URL: https://www.ncbi.nlm.nih.gov/books/NBK50789743. Fields B.N., Byers K. The genetic basis of viral virulence. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 1983, vol. 303, no. 1114, pp. 209–218.44. Godet A.N., Soignon G., Koubi H., Bonnafous P., Agut H., Poirot C., Gautheret-Dejean A. Presence of HHV-6 genome in spermatozoa in a context of couples with low fertility: what type of infection? Andrologia, 2015, vol. 47, no. 5, pp. 531–535. doi: 10.1111/and.1229945. Gonzalez-Scarano F., Beaty B., Sundin D., Janssen R., Endres M.J., Nathanson N. Genetic determinants of the virulence and infectivity of La Crosse virus. Microb. Pathog., 1988, vol. 4, no. 1, pp. 1–7. doi: 10.1016/0882-4010(88)90041-146. Hubacek P., Hrdlickova A., Spacek M., Zajac M., Muzikova K., Sedlacek P., Cetkovsky P. Prevalence of chromosomally integrated HHV-6 in patients with malignant disease and healthy donors in the Czech Republic. Folia Microbiol. (Praha), 2013, vol. 58, no. 1, pp. 87–90. doi: 10.1007/s12223-012-0180-z47. Jaan A., Rajnik M. TORCH Complex. In: Treasure Island (FL). StatPearls Publishing, 2020. URL: https://www.ncbi.nlm.nih.gov/books/NBK56052848. Jain P., Jain A., Khan D.N., Kumar M. Human parvovirus B19 associated dilated cardiomyopathy. BMJ Case Reports, 2013: bcr2013010410. doi: 10.1136/bcr-2013-01041049. Jain P., Jain A., Prakash S., Khan D.N., Singh D.D., Kumar A., Moulik N.R., Chandra T. Prevalence and genotypic characterization of human parvovirus B19 in children with hemato-oncological disorders in North India. J. Med. Virol., 2015, vol. 87, no. 2, pp. 303–309. doi: 10.1002/jmv.2402850. James S.H., Kimberlin D.W. Neonatal herpes simplex virus infection: epidemiology and treatment. Clinics Perinatol., 2015, vol. 42, no. 1, pp. 47–59. doi: 10.1016/j.clp.2014.10.00551. James S.H., Kimberlin D.W. Neonatal herpes simplex virus infection. Infect. Dis. Clin. North Am., 2015, vol. 29, no. 3, pp. 391– 400. doi: 10.1016/j.idc.2015.05.00152. Kaufer B.B., Flamand L. Chromosomally integrated HHV-6: impact on virus, cell and organismal biology. Curr. Opin. Virol., 2014, vol. 9, pp. 111–118. doi: 10.1016/j.coviro.2014.09.01053. Kimberlin D.W., Lin C.Y., Jacobs R.F., Powell D.A., Frenkel L.M., Gruber W.C., Rathore M., Bradley J.S., Diaz P.S., Kumar M., Arvin A.M., Gutierrez K., Shelton M., Weiner L.B., Sleasman J.W., de Sierra T.M., Soong S.J., Kiell J., Lakeman F.D., Whitley R.J.; Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics, 2001, vol. 108, no. 2, pp. 223–229. doi: 10.1542/peds.108.2.22354. Kreilmeier T., Mejri D., Hauck M., Kleiter M., Holzmann K. Telomere transcripts target telomerase in human cancer cells. Genes (Basel), 2016, vol. 7, no. 8: 46. doi: 10.3390/genes708004655. Leong H.N., Tuke P.W., Tedder R.S., Khanom A.B., Eglin R.P., Atkinson C.E., Ward K.N., Griffiths P.D., Clark D.A. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J. Med. Virol., 2007, vol. 79, no. 1, pp. 45–51. doi: 10.1002/jmv.2076056. Lindenburg I.T., Smits-Wintjens V.E., van Klink J.M., Verduin E., van Kamp I.L., Walther F.J., Schonewille H., Doxiadis I.I., Kanhai H.H., van Lith J.M., van Zwet E.W., Oepkes D., Brand A., Lopriore E; LOTUS study group. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study. Am. J. Obstet. Gynecol., 2012, vol. 206, no. 2, pp. 141.e1–141.e8. doi: 10.1016/j.ajog.2011.09.02457. Looker K.J., Magaret A.S., May M.T., Turner K.M.E., Vickerman P., Newman L.M., Gottlieb S.L. First estimates of the global and regional incidence of neonatal herpes infection. Lancet Glob. Health., 2017, vol. 5, no. 3, pp. e300–e309. doi: 10.1016/s2214-109x(16)30362-x58. Luppi M., Barozzi P., Marasca R., Torelli G. Integration of human herpesvirus-6 (HHV-6) genome in chromosome 17 in two lymphoma patients. Leukemia, 1994, vol. 8, no. 1, pp. 41–45.59. Luppi M., Marasca R., Barozzi P., Ferrari S., Ceccherini-Nelli L., Batoni G., Merelli E., Torelli G. Three cases of human herpesvirus-6 latent infection: integration of viral genome in peripheral blood mononuclear cell DNA. J. Med. Virol., 1993, vol. 40, no. 1, pp. 44–52. doi: 10.1002/jmv.189040011060. Lurain N.S., Kapell K.S., Huang D.D., Short J.A., Paintsil J., Winkfield E., Benedict C.A., Ware C.F., Bremer J.W. Human cytomegalovirus UL144 open reading frame: sequence hypervariability in low-passage clinical isolates. J. Virol., 1999, vol. 73, no. 12, pp. 10040–10050. doi: 10.1128/JVI.73.12.10040-10050.199961. Maisonneuve E., Garel C., Friszer S., Pénager C., Carbonne B., Pernot F., Rozenberg F., Schnuriger A., Cortey A., Moutard M.L., Jouannic J.M. Fetal brain injury associated with parvovirus B19 congenital infection requiring intrauterine transfusion. Fetal. Diagn. Ther., 2019, vol. 46, no. 1, pp. 1–11. doi: 10.1159/00048988162. Manandhar T., Hò G.T., Pump W.C., Blasczyk R., Bade-Doeding C. Battle between host immune cellular responses and HCMV immune evasion. Int. J. Mol. Sci., 2019, vol. 20, no. 15: 3626. doi: 10.3390/ijms2015362663. Manuel O., Asberg A., Pang X., Rollag H., Emery V.C., Preiksaitis J.K., Kumar D., Pescovitz M.D., Bignamini A.A., Hartmann A., Jardine A.G., Humar A. Impact of genetic polymorphisms in cytomegalovirus glycoprotein B on outcomes in solid-organ transplant recipients with cytomegalovirus disease. Clin. Infect. Dis., 2009, vol. 49, no. 8, pp. 1160–1166. doi: 10.1086/60563364. Mao H., Rosenthal K.S. Strain-dependent structural variants ofherpes simplex virus type 1 ICP34.5 determine viral plaque size, efficiency of glycoprotein processing, and viral release and neuroinvasive disease potential. J. Virol., 2003, vol. 77, no. 6., pp. 3409–3417. doi: 10.1128/JVI.77.6.3409-3417.200365. Martí-Carreras J., Maes P. Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: revision and future challenges. Virus Genes, 2019, vol. 55, no. 2, pp. 138–164. doi: 10.1007/s11262-018-1627-366. McSharry B.P., Avdic S., Slobedman B. Human cytomegalovirus encoded homologs of cytokines, chemokines and their receptors: roles in immunomodulation. Viruses, 2012, vol. 4, no. 11, pp. 2448–2470. doi: 10.3390/v411244867. Mercolini F., Verdi F., Eisendle K., Messner H., Staffler A. Congenital disseminated HSV-1 infection in preterm twins after primary gingivostomatitis of the mother: case report and review of the literature. Z. Geburtshilfe Neonatol., 2014, vol. 218, no. 6, pp. 261–264. doi: 10.1055/s-0034-138585468. Michou V., Liarmakopoulou S., Thomas D., Tsimaratou K., Makarounis K., Constantoulakis P., Angelopoulou R., Tsilivakos V. Herpes virus infected spermatozoa following density gradient centrifugation for IVF purposes. Andrologia, 2012, vol. 44, no. 3, pp. 174–180. doi: 10.1111/j.1439-0272.2010.01121.x69. Miura H., Kawamura Y., Hattori F., Kozawa K., Ihira M., Ohye T., Kurahashi H., Yoshikawa T. Chromosomally integrated human herpesvirus 6 in the Japanese population. J. Med. Virol., 2018, vol. 90, no. 10, pp. 1636–1642. doi: 10.1002/jmv.2524470. Mühlemann B., Margaryan A., Damgaard P.B., Allentoft M.E., Vinner L., Hansen A.J., Weber A., Bazaliiskii V.I., Molak M., Arneborg J., Bogdanowicz W., Falys C., Sablin M., Smrčka V., Sten S., Tashbaeva K., Lynnerup N., Sikora M., Smith D.J., Fouchier R.A.M., Drosten C., Sjögren K.G., Kristiansen K., Willerslev E., Jones T.C. Ancient human parvovirus B19 in Eurasia reveals its long-term association with humans. Proc. Natl. Acad. Sci. USA, 2018, vol. 115, no. 29, pp. 7557–7562. doi: 10.1073/pnas.180492111571. Müller V., Fraser C., Herbeck J.T. A strong case for viral geneticfactors in HIV virulence. Viruses, 2011, vol. 3, no. 3, pp. 204–216. doi: 10.3390/v3030204.1772. Murayama T., Takegoshi M., Tanuma J., Eizuru Y. Analysis of human cytomegalovirus UL144 variability in low-passage clinical isolates in Japan. Intervirology, 2005, vol. 48, no. 2–3, pp. 201–206. doi: 10.1159/00008174973. Mussi-Pinhata M.M., Yamamoto A.Y., Aragon D.C., Duarte G., Fowler K.B., Boppana S., Britt W.J. Seroconversion for cytomegalovirus infection during pregnancy and fetal infection in a highly seropositive population: “The brachs study”. J. Infect. Dis., 2018, vol. 218, no. 8, pp. 1200–1204. doi: 10.1093/infdis/jiy32174. Naing Z., Hamilton S.T., van Zuylen W.J., Scott G.M., Rawlinson W.D. Differential expression of PDGF receptor-α in human placental trophoblasts leads to different entry pathways by human cytomegalovirus strains. Sci. Rep., 2020, vol. 10, no. 1: 1082. doi: 10.1038/s41598-020-57471-375. Nelson J.A., Fleckenstein B., Jahn G., Galloway D.A., McDougall J.K. Structure of the transforming region of human cytomegalovirus AD169. J. Virol., 1984, vol. 49, no. 1, pp. 109–115. doi: 10.1128/JVI.49.1.109-115.198476. Nijman J., Mandemaker F.S., Verboon-Maciolek M.A., Aitken S.C., van Loon A.M., de Vries L.S., Schuurman R. Genotype distribution, viral load and clinical characteristics of infants with postnatal or congenital cytomegalovirus infection. PLoS One, 2014, vol. 9, no. 9: e108018. doi: 10.1371/journal.pone.010801877. Novak Z., Ross S.A., Patro R.K., Pati S.K., Kumbla R.A., Brice S., Boppana S.B. Cytomegalovirus strain diversity in seropositive women. J. Clin. Microbiol., 2008, vol. 46, no. 3, pp. 882–886. doi: 10.1128/JCM.01079-0778. Pantry S.N., Medveczky M.M., Arbuckle J.H., Luka J., Montoya J.G., Hu J., Renne R., Peterson D., Pritchett J.C., Ablashi D.V., Medveczky P.G. Persistent human herpesvirus-6 infection in patients with an inherited form of the virus. J. Med. Virol., 2013, vol. 85, no. 11, pp. 1940–1946. doi: 10.1002/jmv.2368579. Pantry S.N., Medveczky P.G. Latency, integration, and reactivation of human herpesvirus-6. Viruses, 2017, vol. 9, no. 7: 194. doi: 10.3390/v907019480. Paradowska E., Studzińska M., Nowakowska D., Wilczyński J., Rycel M., Suski P., Gaj Z., Kaczmarek B., Zbróg Z., Leśnikowski Z.J. Distribution of UL144, US28 and UL55 genotypes in Polish newborns with congenital cytomegalovirus infections. Eur. J. Clin. Microbiol. Infect Dis., 2012, vol. 31, no. 7, pp. 1335–1345. doi: 10.1007/s10096-011-1447-z81. Pellett P.E., Ablashi D.V., Ambros P.F., Agut H., Caserta M.T., Descamps V., Flamand L., Gautheret-Dejean A., Hall C.B., Kamble R.T., Kuehl U., Lassner D., Lautenschlager I., Loomis K.S., Luppi M., Lusso P., Medveczky P.G., Montoya J.G., Mori Y., Ogata M., Pritchett J.C., Rogez S., Seto E., Ward K.N., Yoshikawa T., Razonable R.R. Chromosomally integrated human herpesvirus 6: questions and answers. Rev. Med. Virol., 2012, vol. 22, no. 3, pp. 144–155. doi: 10.1002/rmv.71582. Pickett B.E., Sadat E.L., Zhang Y., Noronha J.M., Squires R.B., Hunt V., Liu M., Kumar S., Zaremba S., Gu Z., Zhou L., Larson C.N., Dietrich J., Klem E.B., Scheuermann R.H. ViPR: an open bioinformatics database and analysis resource for virology research. Nucleic Acids Res., 2012, vol. 40, no. D1, pp. D593–D598. doi: 10.1093/nar/gkr85983. Pignatelli S., Lazzarotto T., Gatto M.R., Dal Monte P., Landini M.P., Faldella G., Lanari M. Cytomegalovirus gN genotypes distribution among congenitally infected newborns and their relationship with symptoms at birth and sequelae. Clin. Infect. Dis., 2010, vol. 51, no. 1, pp. 33–41. doi: 10.1086/65342384. Pinninti S.G., Kimberlin D.W. Management of neonatal herpes simplex virus infection and exposure. Arch. Dis. Child. Fetal Neonatal Ed., 2014, vol. 99, no. 3, pp. 240–244. doi: 10.1136/archdischild-2013-30376285. Plummer F.A., Hammond G.W., Forward K., Sekla L., Thompson L.M., Jones S.E., Kidd I.M., Anderson M.J. An erythema infectiosum-like illness caused by human parvovirus infection. N. Engl. J. Med., 1985, vol. 313, no. 2, pp. 74–79. doi: 10.1056/NEJM19850711313020386. Renner D.W., Szpara M.L. Impacts of genome-wide analyses on our understanding of human herpes-virus diversity and evolution. J. Virol., 2018, vol. 92, no. 1: e00908-17. doi: 10.1128/JVI.00908-1787. Renzette N., Gibson L., Jensen J.D., Kowalik T.F. Human cytomegalovirus intrahost evolution — a new avenue for understanding and controlling herpesvirus infections. Curr. Opin. Virol., 2014, vol. 8, pp. 109–115. doi: 10.1016/j.coviro.2014.08.001.2688. Revello M.G., Campanini G., Piralla A., Furione M., Percivalle E., Zavattoni M., Gerna G. Molecular epidemiology of primary human cytomegalovirus infection in pregnant women and their families. J. Med. Virol., 2008, vol. 80, no. 8, pp. 1415–1425. doi: 10.1002/jmv.2124389. Ribbert H. Ueber protozoenartige Zellen in der Niere eines syphilitischen Neugeborenen und in der Parotis von Kindern. Zbl. Allg. Pathol., 1904, vol. 15, pp. 945–948.90. Rinckel L.A., Buno B.R., Gierman T.M., Lee D.C. Discovery and analysis of a novel parvovirus B19 genotype 3 isolate in the United States. Transfusion, 2009, vol. 49, no. 7, pp. 1488–1492. doi: 10.1111/j.1537-2995.2009.02160.x91. Robinson C.M., Jesudhasan P.R., Pfeiffer J.K. Bacterial lipopolysaccharide binding enhances virion stability and promotes environmental fitness of an enteric virus. Cell Host Microbe, 2014, vol. 15, no. 1, pp. 36–46. doi: 10.1016/j.chom.2013.12.004.13–1892. Rowe W.P., Hartley J.W., Waterman S., Turner H.C., Huebner R.J. Cytopathogenic agent resembling human salivary gland virus recovered from tissue cultures of human adenoids. Proc. Soc. Exp. Biol. Med., 1956, vol. 92, no. 2, pp. 418–424. doi: 10.3181%2F00379727-92-2249793. Sakaoka H., Kawana T., Grillner L., Aomori T., Yamiguchi T., Saito H., Fujinaga K. Genome variations in herpes simplex virus type 2 strains isolated in Japan and Sweden. J. Gen. Virol., 1987, vol. 68, no. 8, pp. 2105–2116. doi: 10.1099/0022-1317-68-8-2105.2194. Sakaoka H., Kurita K., Iida Y., Takada S., Umene K., Kim Y.T., Ren C.S., Nahmias A.J. Quantitative analysis of genomic polymorphism of herpes simplex virus type 1 strains from six countries: studies of molecular evolution and molecular epidemiology of the virus. J. Gen. Virol., 1994, vol. 75, no. 3, pp. 513–527. doi: 10.1099/0022-1317-75-3-513.2295. Salbetti M.B., Pedranti M.S., Barbero P., Molisani P., Lazzari M., Olivera N., Isa M.B., Bertoldi A., Moreno L., Adamo M.P. Molecular screening of the human parvoviruses B19 and bocavirus 1 in the study of congenital diseases as applied to symptomatic pregnant women and children. Access Microbiol., 2019, vol. 1, no. 5: e000037. doi: 10.1099/acmi.0.00003796. Sanabani S., Neto W.K., Pereira J., Sabino E.C. Sequence variability of human erythroviruses present in bone marrow of Brazilian patients with various parvovirus B19-related hematological symptoms. J. Clin. Microbiol., 2006, vol. 44, no. 2, pp. 604–606. doi: 10.1128/JCM.44.2.604-606.200697. Sénat M.V., Anselem O., Picone O., Renesme L., Sananès N., Vauloup-Fellous C., Sellier Y., Laplace J.P., Sentilhes L. Prevention and management of genital herpes simplex infection during pregnancy and delivery: guidelines from the french college of gynaecologists and obstetricians (CNGOF). Eur. J. Obstet. Gynecol. Reprod. Biol., 2018, vol. 224, pp. 93–101. doi: 10.1016/j.ejogrb.2018.03.01198. Servant A., Laperche S., Lallemand F., Marinho V., De Saint Maur G., Meritet J.F., Garbarg-Chenon A. Genetic diversity within human erythroviruses: identification of three genotypes. J. Virol., 2002, vol. 76, no. 18, pp. 9124–9134. doi: 10.1128/jvi.76.18.9124-9134.200299. Sharma S., Wisner T.W., Johnson D.C., Heldwein E.E. HCMV gB shares structural and functional properties with gB proteins from other herpesviruses. Virology, 2013, vol. 435, no. 2, pp. 239–249. doi: 10.1016/j.virol.2012.09.024100. Slavov S.N., Kashima S., Silva-Pinto A.C., Covas D.T. Genotyping of Human parvovirus B19 among Brazilian patients with hemoglobinopathies. Can. J. Microbiol., 2012, vol. 58, no. 2, pp. 200–205. doi: 10.1139/w11-119101. Smith M.G. Propagation in tissue cultures of a cytopathogenic virus from human salivary gland virus (SGV) disease. Proc. Soc. Exp. Biol. Med., 1956, vol. 92, no. 2, pp. 424–430. doi: 10.3181/00379727-92-22498102. Sowmya P., Dhanya V., Madhavan H.N., Therese K.L. Comparative efficacy of PCR-based restriction fragment length polymorphism (RFLP) & multiplex PCR for glycoprotein B (gB) genotyping of human cytomegalovirus. Indian J. Med. Res., 2007, vol. 126, no. 2, pp. 122–127.103. Staras S.A., Dollard S.C., Radford K.W., Flanders W.D., Pass R.F., Cannon M.J. Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clin. Infect. Dis., 2006, vol. 43, no. 9, pp. 1143–1151. doi: 10.1086/508173104. Stranska R., Schuurman R., Toet M., Verboon-Maciolek M., de Vries L.S., van Loon A.M. Application of UL144 molecular typing to determine epidemiology of cytomegalovirus infections in preterm infants. J. Clin. Microbiol., 2006, vol. 44, no. 3, pp. 1108– 1110. doi: 10.1128/JCM.44.3.1108-1110.2006105. Tanaka-Taya K., Sashihara J., Kurahashi H., Amo K., Miyagawa H., Kondo K., Okada S., Yamanishi K. Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA. J. Med. Virol., 2004, vol. 73, no. 3, pp. 465–473. doi: 10.1002/jmv.20113106. Telford M., Navarro A., Santpere G. Whole genome diversity of inherited chromosomally integrated HHV-6 derived from healthy individuals of diverse geographic origin. Sci. Rep., 2018, vol. 8, no. 1: 3472. doi: 10.1038/s41598-018-21645-x107. Trincado D.E., Scott G.M., White P.A., Hunt C., Rasmussen L., Rawlinson W.D. Human cytomegalovirus strains associated with congenital and perinatal infections. J. Med. Virol., 2000, vol. 61, no. 4, pp. 481–487. doi: 10.1002/1096-9071(200008) 61:4<481::aidjmv11>3.0.co;2-h108. Tscherne D.M., García-Sastre A. Virulence determinants of pandemic influenza viruses. J. Clin. Investig., 2011, vol. 121, no. 1, pp. 6–13. doi: 10.1172/JCI44947.16109. Wang C., Zhao L., Lu S. Role of TERRA in the regulation of telomere length. Int. J. Biol. Sci., 2015, vol. 11, no. 3, pp. 316–323. doi: 10.7150/ijbs.10528110. Waring G.J. Parvovirus B19 infection: timely diagnosis in pregnancy essential. Case Rep. in Women’s Health, 2018, vol. 18: e00057. doi: 10.1016/j.crwh.2018.e00057111. Warnecke J.M., Pollmann M., Borchardt-Lohölter V., Moreira-Soto A., Kaya S., Sener A.G., Gómez-Guzmán E., FigueroaHernández L., Li W., Li F., Buska K., Zakaszewska K., Ziolkowska K., Janz J., Ott A., Scheper T., Meyer W. Seroprevalences of antibodies against TORCH infectious pathogens in women of childbearing age residing in Brazil, Mexico, Germany, Poland, Turkey and China. Epidemiol. Infect., 2020, vol. 30, no. 148: e271. doi: 10.1017/S0950268820002629112. Whitley R., Arvin A., Prober C., Burchett S., Corey L., Powell D., Plotkin S., Starr S., Alford C., Connor J., Jacobs R., Nahmias A., Soong S.-J. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. N. Engl. J. Med., 1991, vol. 324, no. 7, pp. 444–449. doi: 10.1056/nejm199102143240703113. Whitley R., Arvin A., Prober C., Corey L., Burchett S., Plotkin S., Starr S., Jacobs R., Powell D., Nahmias A., Sumaya C., Edwards K., Alford C., Caddell G., Soong S.-J. Predictors of morbidity and mortality in neonates with herpes simplex virus infections. N. Engl. J. Med., 1991, vol. 324, no. 7, pp. 450–454. doi: 10.1056/NEJM199102143240704114. Xiong Y.Q., Tan J., Liu Y.M., He Q., Li L., Zou K., Sun X. The risk of maternal parvovirus B19 infection during pregnancy on fetal loss and fetal hydrops: a systematic review and meta-analysis. J. Clin. Virol., 2019, no. 114, pp. 12–20. doi: 10.1016/j.jcv.2019.03.004115. Yan H., Koyano S., Inami Y., Yamamoto Y., Suzutani T., Mizuguchi M., Ushijima H., Kurane I., Inoue N. Genetic variations in the gB, UL144 and UL149 genes of human cytomegalovirus strains collected from congenitally and postnatally infected Japanese children. Arch. Virol., 2008, vol. 153, no. 4, pp. 667–674. doi: 10.1007/s00705-008-0044-7116. Zhi N., Zádori Z., Brown K.E., Tijssen P. Construction and sequencing of an infectious clone of the human parvovirus B19. Virology, 2004, vol. 318, no. 1, pp. 142–152. doi: 10.1016/j.virol.2003.09.011117. Zuhair M., Smit G.S.A., Wallis G., Jabbar F., Smith C., Devleesschauwer B., Griffiths P. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev. Med. Virol., 2019, vol. 29, no. 3: e2034. doi: 10.1002/rmv.2034