DISTRIBUTION OF CYTOMEGALOVIRUS GENOTYPES CIRCULATING AMONG NEWBORN CHILDREN OF ST. PETERSBURG

  • Authors: Igolkina A.1, Kusakin A.2, Markin I.3, Goleva O.2, Chukhlovin A.4, Baziian E.2, Eismont Y.A.2, Rogozina N.V.3,5, Vasilev V.V.3,6, Glotov O.S.7
  • Affiliations:
    1. Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases under the Federal Medical Biological Agency
    2. FGBU «Pediatric Research and Clinical Center for Infectious Diseases»
    3. Pediatric Research and Clinical Center for Infectious Diseases
    4. R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantology, Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia 197089, Russian Federation, St. Petersburg, L. Tolstoy str., 6/8, R. Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantology, Pavlov First St. Petersburg State Medical University. Phone/fax: +7 (812) 499-70-79
    5. St. Petersburg State Pediatric Medical University
    6. North-Western State Medical University named after I.I. Mechnikov
    7. FGBU «Pediatric Research and Clinical Center for Infectious Diseases» D.O. Ott’s Research Institute Institute of Obstetrics, Gynecology, and Reproductology
  • Section: ORIGINAL ARTICLES
  • Submitted: 14.11.2024
  • Accepted: 23.03.2025
  • URL: https://iimmun.ru/iimm/article/view/17814
  • DOI: https://doi.org/10.15789/2220-7619-DOC-17814
  • ID: 17814


Cite item

Full Text

Abstract

The aim of the present study was to perform genotyping of the three most polymorphic regions in the cytomegalovirus (CMV) genome, i.e., UL55 (gB), UL73 (gN), UL75 (gH) in newborns with congenital cytomegalovirus infection (CMVI), to determine distribution of genotypes circulating in the current cohort of patients in St. Petersburg and to compare them with those of CMV circulating in the Russian Federation and worldwide. The study was performed at the Pediatric Research and Clinical Center for Infectious Diseases at the Federal Medical Biological Agency. The study included 61 blood, saliva, urine DNA samples isolated from 26 infants with clinical manifestations of congenital CMV. Molecular genetic methods were used as follows:  DNA isolation from biological samples; qualitative detection of CMV DNA by amplification of specific viral DNA fragment using real-time PCR detection of amplicons, preparation of sequencing libraries enriched by hybridization with labeled oligonucleotides. The obtained results of DNA sequencing were processed using bioinformatics methods. According to the results of our study, it was shown that the sequencing of viral DNA segments from various biological samples has yielded different results on CMV genetic polymorphisms. For instance, the genotypes of all three studied regions with satisfactory coverage (according to sequencing data) were obtained more often in urine and saliva than in peripheral blood samples. When analyzing the distribution of genotypes in the UL55 region, the genotype gB7 prevailed being determined in 50% of newborn patients. Analysis of the obtained UL73 region sequencing data allowed to identify the dominant gN4c genotype (37.5%). According to the sequencing results for UL75 region of CMV encoding glycoprotein H, the genotypes gH1 and gH2 showed equal distribution (by 50%). When comparing the genotypes observed in this study with those obtained in Russia and worldwide, some differences in the nucleotide sequence were revealed for the specified regions of CMV genome. Phylogenetic analysis of CMV made it possible to illustrate heterogeneity of gene variant distribution among newborn children in St. Petersburg.

About the authors

Aleksandra Igolkina

Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases under the Federal Medical Biological Agency

Email: gribanovaalal@bk.ru
ORCID iD: 0009-0000-4310-9741

post-graduate student of the department of experimental medical virology, molecular genetics and biobanking

Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9

Aleksey Kusakin

FGBU «Pediatric Research and Clinical Center for Infectious Diseases»

Email: kusakinax@gmail.com
ORCID iD: 0000-0001-9546-7831

research assistant of the department of experimental medical virology, molecular genetics and biobanking

197022, Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9

Ivan Markin

Pediatric Research and Clinical Center for Infectious Diseases

Email: i.v.markin@mail.ru
ORCID iD: 0000-0001-9922-401X

postgraduate student of the department of congenital infectious diseases

197022, Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9

Olga Goleva

FGBU «Pediatric Research and Clinical Center for Infectious Diseases»

Email: golev.ao@mail.ru
ORCID iD: 0000-0003-3285-9699

PhD Senior Scientist, Department of experimental medical virology, molecular genetics and biobanking

197022, Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9

Alexey Chukhlovin

R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantology, Pavlov First St. Petersburg State Medical University, St. Petersburg, Russia 197089, Russian Federation, St. Petersburg, L. Tolstoy str., 6/8,
R. Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantology, Pavlov First St. Petersburg State Medical University. Phone/fax: +7 (812) 499-70-79

Email: alexei.chukh@mail.ru
ORCID iD: 0000-0002-9449-574X

PhD (Medicine), Professor, R. Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantology, Pavlov First St. Petersburg State Medical University, St. Petersburg, Russian Federation

Россия

Elena Baziian

FGBU «Pediatric Research and Clinical Center for Infectious Diseases»

Email: waz2107gen@yandex.ru
ORCID iD: 0000-0001-7837-3315

Junior researcher Department for experimental medical virology, molecular genetics and biobanking 

197022, Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9;

Yurii A. Eismont

FGBU «Pediatric Research and Clinical Center for Infectious Diseases»

Email: y-eis@inbox.ru
ORCID iD: 0000-0002-4828-8053

PhD Senior Scientist, Department of experimental medical virology, molecular genetics and biobanking

197022, Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9;

Natalia V. Rogozina

Pediatric Research and Clinical Center for Infectious Diseases; St. Petersburg State Pediatric Medical University

Email: lelekin96@mail.ru
ORCID iD: 0000-0003-0968-6291

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

St. Petersburg 

Россия

Valeriy V. Vasilev

Pediatric Research and Clinical Center for Infectious Diseases; North-Western State Medical University named after I.I. Mechnikov

Email: vcubed@ya.ru
ORCID iD: 0000-0003-2579-2799

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 

Россия

Oleg S. Glotov

FGBU «Pediatric Research and Clinical Center for Infectious Diseases»

D.O. Ott’s Research Institute Institute of Obstetrics, Gynecology, and Reproductology

Author for correspondence.
Email: olglotov@mail.ru
ORCID iD: 0000-0002-0091-2224

Doctor of Science in Biology, Head of Department of experimental medical virology, molecular genetics and biobanking of Federal State-Financed Institution Pediatric Research and Clinical Center for Infectious Diseases;

Senior Researcher at the Department of Genomic Medicine, D.O. Ott’s Research Institute Institute of Obstetrics, Gynecology, and Reproductology

197022, Россия, г. Санкт-Петербург, ул. Профессора Попова, д. 9

References

  1. Ванькова О. Е., Алексеева А. Е., Бруснигина Н. Ф. Молекулярное типирование цитомегаловирусов, циркулирующих среди населения Нижнего Новгорода // Молекулярная диагностика 2017 : сборник трудов IХ Всероссийской научно-практической конференции с международным участием. 2017. Vol. 2. P. 310–311. Vankova O. E., Alekseeva A. E., Brusnigina N. F. Molecular typing of cytomegaloviruses circulating among the population of Nizhny Novgorod // Molecular diagnostics 2017: collection of proceedings of the IX All-Russian scientific and practical conference with RIAC. 2017. Vol. 2. pp. 310–311. chrome extension://efaidnbmnnnibpcajpcglclefindmkaj/https://kpfu.ru/staff_files/F1634184337/Tom_2_s_oblozhkoj.pdf
  2. Ванькова О.Е., Бруснигина Н.Ф. Молекулярная и филогенетическая характеристика изолятов цитомегаловируса, выделенных у детей Нижнего Новгорода. Здоровье населения и среда обитания – ЗНиСО. 2021;(4):25-30. https://doi.org/10.35627/2219-5238/2021-337-4-25-30. Vankova O.E., Brusnigina N.F. Molecular and Phylogenetic Characteristics of Cytomegaloviruses Isolated from Children in Nizhny Novgorod. Public Health and Life Environment – PH&LE. 2021;(4):25-30. (In Russ.) https://doi.org/10.35627/2219-5238/2021-337-4-25-30 https://doi.org/10.35627/2219-5238/2021-337-4-25-30
  3. Ванькова О.Е., Бруснигина Н.Ф. Генотипирование клинических изолятов цитомегаловируса, выделенных у реципиентов солидных органов // Инфекция и иммунитет. - 2022. - Т. 12. - №1. - C. 59-68. doi: 10.15789/2220-7619-GCC-1653. Vankova O.E., Brusnigina N.F. Genotyping clinical cytomegalovirus isolates in solid-organs-transplant recipients // Russian Journal of Infection and Immunity. - 2022. - Vol. 12. - N. 1. - P. 59-68. doi: 10.15789/2220-7619-GCC-1653 doi: 10.15789/2220-7619-GCC-1653
  4. Ванькова О.Е., Бруснигина Н.Ф., Новикова Н.А. NGS-технология в мониторинге генетического разнообразия штаммов цитомегаловируса // Соврем. технол. мед. 2023; 15(2): 41, https://doi.org/10.17691/stm2023.15.2.04 Vankova O.E., Brusnigina N.F., Novikova N.A. NGS technology in monitoring the genetic diversity of cytomegalovirus strains. Sovremennye tehnologii v medicine 2023; 15(2): 41, https://doi.org/10.17691/stm2023.15.2.04 https://doi.org/10.17691/stm2023.15.2.04
  5. Васильев В.В., Рогозина Н.В., Маркин И.В. Современные представления о механизмах развития врожденной цитомегаловирусной инфекции. Журнал инфектологии. 2023;15(2):35-46. https://doi.org/10.22625/2072-6732-2023-15-2-35-46. Vasil’ev V.V., Rogozina N.V., Markin I.V. Modern concepts of the mechanisms of congenital cytomegalovirus infection development. Journal Infectology. 2023;15(2):35-46. (In Russ.) https://doi.org/10.22625/2072-6732-2023-15-2-35-46
  6. https://doi.org/10.22625/2072-6732-2023-15-2-35-46.
  7. Демин М.В., Тихомиров Д.С., Бидерман Б.В., Глинщикова О.А., Дроков М.Ю., Судариков А.Б. и др. Мутации в гене UL97 цитомегаловируса, ассоциированные с устойчивостью к ганцикловиру, у реципиентов аллогенных гемопоэтических стволовых клеток. Клиническая микробиология и антимикробная химиотерапия. 2019; 21(4): 352–7. https://doi.org/10.36488/ cmac.2019.4.352-357. Demin M.V., Tikhomirov D.S., Biderman B.V., Glinshchikova O.A., Drokov M.Yu., Sudarikov A.B., et al. Mutations in the cytomegalovirus UL97 gene associated with ganciclovir resistance in recipients of allogeneic hematopoietic stem cell transplants. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya. 2019; 21(4): 352–7. https://doi.org/10.36488/cmac.2019.4.352-357 https://doi.org/10.36488/ cmac.2019.4.352-357.
  8. Рогозина Н.В., Васильев В.В., Иванова Р.А., Ушакова Г.М., Безверхая Н.С. Поражения органов и систем у детей, родившихся от матерей с острой цитомегаловирусной инфекцией // Инфекционные болезни: новости, мнения, обучение. 2023. Т. 12, № 2. С. 57-64. DOI: https://doi.org/10.33029/2305-3496-2023-12-2-57-64. Rogozina N.V., Vasil’ev V.V., Ivanova R.A., Ushakova G.M., Bezverkhaya N.S. Lesions of organs and systems in children born from mothers with acute cytomegalovirus infection. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2023; 12 (2): 57–64. DOI: https://doi.org/10.33 029/2305-3496-2023-12-2-57-64 https://doi.org/10.33029/2305-3496-2023-12-2-57-64.
  9. Шахгильдян В.И., Александрова Е.П., Козырина Н.В., Шипулина О.Ю., Додонова Э.А., Шахгильдян Н.В. Цитомегаловирусная инфекция у беременных и новорожденных: эпидемиологический анализ, новые подходы к диагностике и лечению // Акушерство и гинекология: новости, мнения, обучение. 2020. Т. 8, № 2. С. 80-94. doi: 10.24411/2303-9698-2020-12008. Shakhgildyan V.I., Alexandrova E.P., Kozyrina N.V., Shipulina O.Yu., Domonova E.A., Shakhgildian N.V. Cytomegalovirus infection in pregnant women and newborns: epidemiological analysis, new approaches to diagnosis and treatment. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2020; 8 (2): С. 80–94. doi: 10.24411/2303-9698-2020-12008 doi: 10.24411/2303-9698-2020-12008.
  10. Лобзин Ю.В., Жданов К.В., Руководство по инфекционным болезням в 2 кн. Кн.2. 2011. 744 p. Lobzin Yu.V., Zhdanov K.V., Guide to infectious diseases in 2 books. Book 2. 2011. 744 p.
  11. Ahmad J, Sayedy N, Sanivarapu R, Akella J, Iqbal J. CMV Pancreatitis in an Immunocompromised Patient. Case Rep Crit Care. 2021 Feb 19; 2021:8811396. doi: 10.1155/2021/8811396. doi: 10.1155/2021/8811396.
  12. Dong N, Cao L, Su L, Lu L, Dong Z, Xu M, Xu J. Human cytomegalovirus envelope glycoprotein B, H, and N polymorphisms among infants of Shanghai area in China. J Med Virol. 2020 Dec;92(12):3674-3681. doi: 10.1002/jmv.26210. doi: 10.1002/jmv.26210.
  13. Dong N, Cao L, Zheng D, Su L, Lu L, Dong Z, Xu M, Xu J. Distribution of CMV envelope glycoprotein B, H and N genotypes in infants with congenital cytomegalovirus symptomatic infection. Front Pediatr. 2023 Mar 15;11:1112645. doi: 10.3389/fped.2023.1112645. doi: 10.3389/fped.2023.1112645.
  14. Fernandez, C., Chasqueira, MJ., Marques, A. et al. Lower prevalence of congenital cytomegalovirus infection in Portugal: possible impact of COVID-19 lockdown?. Eur J Pediatr 181, 1259–1262 (2022). https://doi.org/10.1007/s00431-021-04271-0 https://doi.org/10.1007/s00431-021-04271-0
  15. Grgic I, Gorenec L. Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review. Trop Med Infect Dis. 2024 Feb 15;9(2):49. doi: 10.3390/tropicalmed9020049. doi: 10.3390/tropicalmed9020049.
  16. Hu H, Cheng Y, Peng Q, Chen K. Clinical Features, Treatment Courses, and Distribution of Cytomegalovirus Genotypes among Thrombocytopenia Patients Aged Younger than 12 Months. Am J Perinatol. 2021 Nov;38(13):1403-1411. doi: 10.1055/s-0040-1713001. doi: 10.1055/s-0040-1713001.
  17. Hu H, Peng W, Peng Q, Cheng Y. Cytomegalovirus Genotype Distribution among Congenital and Perinatal Infected Patients with CMV-Associated Thrombocytopenia. Fetal Pediatr Pathol. 2022 Feb;41(1):77-86. doi: 10.1080/15513815.2020.1765916. doi: 10.1080/15513815.2020.1765916.
  18. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007 Jul-Aug;17(4):253-76. doi: 10.1002/rmv.535. doi: 10.1002/rmv.535.
  19. Min X, Wang L, Cui A, Zhang C, Wang D, Liu Y, Li Z, Xu W. The nucleic acid positive rate and genotype distribution of human cytomegalovirus in human milk banks in China. Arch Virol. 2020 May;165(5):1099-1107. doi: 10.1007/s00705-020-04573-y. doi: 10.1007/s00705-020-04573-y.
  20. Mirsalehi N, Yavarian J, Ghavami N, Naseri M, Khodakhah F, Shatizadeh Malekshahi S, Zadheidar S, Mokhtari-Azad T, Shafiei-Jandaghi NZ. Congenital cytomegalovirus infection in newborns suspected of congenital rubella syndrome in Iran: a cross-sectional study. BMC Pediatr. 2024 Jan 10;24(1):31. doi: 10.1186/s12887-023-04502-3. doi: 10.1186/s12887-023-04502-3.
  21. Mu H, Qiao W, Zou J, Zhang H. Human cytomegalovirus glycoprotein B genotypic distributions and viral load in symptomatic infants. J Infect Dev Ctries. 2023 Dec 31;17(12):1806-1813. doi: 10.3855/jidc.18291. doi: 10.3855/jidc.18291.
  22. Mujtaba G, Khurshid A, Sharif S, Alam MM, Aamir UB, Shaukat S, Angez M, Rana MS, Umair M, Shah AA, Zaidi SS. Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan. PLoS One. 2016 Jul 1;11(7):e0156049. doi: 10.1371/journal.pone.0156049. doi: 10.1371/journal.pone.0156049.
  23. Nguyen CC, Kamil JP. Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism. Viruses. 2018 Dec 11;10(12):704. doi: 10.3390/v10120704. doi: 10.3390/v10120704.
  24. Paradowska E, Jabłońska A, Studzińska M, Kasztelewicz B, Wiśniewska-Ligier M, Dzierżanowska-Fangrat K, Woźniakowska-Gęsicka T, Czech-Kowalska J. Distribution of the CMV glycoprotein gH/gL/gO and gH/gL/pUL128/pUL130/pUL131A complex variants and associated clinical manifestations in infants infected congenitally or postnatally. Sci Rep. 2019 Nov 8;9(1):16352. doi: 10.1038/s41598-019-52906-y. doi: 10.1038/s41598-019-52906-y.
  25. Pignatelli S, Dal Monte P, Rossini G, Landini MP. Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol. 2004 Nov-Dec;14(6):383-410. doi: 10.1002/rmv.438. doi: 10.1002/rmv.438.
  26. Puhakka L, Pati S, Lappalainen M, Lönnqvist T, Niemensivu R, Lindahl P, Nieminen T, Seuri R, Nupponen I, Boppana S, Saxen H. Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection. J Clin Virol. 2020 Apr;125:104287. doi: 10.1016/j.jcv.2020.104287. doi: 10.1016/j.jcv.2020.104287.
  27. Ross SA, Fowler KB, Ashrith G, Stagno S, Britt WJ, Pass RF, Boppana SB. Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity. J Pediatr. 2006 Mar;148(3):332-6. doi: 10.1016/j.jpeds.2005.09.003. doi: 10.1016/j.jpeds.2005.09.003.
  28. Sapuan S, Theodosiou AA, Strang BL, Heath PT, Jones CE. A systematic review and meta-analysis of the prevalence of human cytomegalovirus shedding in seropositive pregnant women. Rev Med Virol. 2022; 32(6):e2399. https://doi.org/10.1002/rmv.2399. https://doi.org/10.1002/rmv.2399.
  29. Sarkar A, Das D, Ansari S, Chatterjee RP, Mishra L, Basu B, Ghosh SK, Bhattacharyay M, Chakraborty N. Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection. BMC Pediatr. 2019 Aug 22;19(1):291. doi: 10.1186/s12887-019-1666-5. doi: 10.1186/s12887-019-1666-5.
  30. Wang HY, Valencia SM, Pfeifer SP, Jensen JD, Kowalik TF, Permar SR. Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity. Viruses. 2021 Jun 9;13(6):1106. doi: 10.3390/v13061106. doi: 10.3390/v13061106.
  31. White JL, Patel EU, Abraham AG, Grabowski MK, Arav-Boger R, Avery RK, Quinn TC, Tobian AAR. Prevalence, Magnitude, and Genotype Distribution of Urinary Cytomegalovirus (CMV) Shedding Among CMV-Seropositive Children and Adolescents in the United States. Open Forum Infect Dis. 2019 Jun 5;6(7):ofz272. doi: 10.1093/ofid/ofz272. doi: 10.1093/ofid/ofz272.
  32. Zuhair M, Smit GSA, Wallis G, et al. Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis. Rev Med Virol. 2019; 29:e2034. https://doi.org/10.1002/rmv.2034. https://doi.org/10.1002/rmv.2034.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) Igolkina A., Kusakin A., Markin I., Goleva O., Chukhlovin A., Baziian E., Eismont Y.A., Rogozina N.V., Vasilev V.V., Glotov O.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies