References

pediatricjournal

Архив педиатрии и детской хирургии

Archives of Pediatrics and Pediatric Surgery

2949-46643033-6783

НИКИ детства Минздрава Московской области

pediatricjournal-211

Research Article

ОБЗОРЫ

REVIEWS

Роль полимеразной цепной реакции в лабораторной диагностике инфекционного мононуклеоза у детей

https://orcid.org/0009-0007-4383-8507

Павленко

Екатерина Валерьевна

pavlenkoev5@gmail.com

https://orcid.org/0000-0001-5540-924X

Бочарова

Ксения Александровна

Bocharova_k@bsuedu.ru

https://orcid.org/0009-0002-5834-9320

Бурцев

Андрей Русланович

andreyburtsev31@gmail.com

Белгородский государственный национально-исследовательский университет, Россия, 308015, г. Белгород, ул. Победы, 85,

2026

05062026

211

2026

Павленко Е.В., Бочарова К.А., Бурцев А.Р.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://journal.nikid.ru/jour/article/view/211

Инфекционный мононуклеоз (ИМ), вызываемый вирусом Эпштейна-Барр (ВЭБ), остается одной из наиболее актуальных проблем педиатрической инфекционологии. Несмотря на относительно благоприятное течение у иммунокомпетентных детей, заболевание требует точной лабораторной верификации для дифференциальной диагностики с острыми лейкозами, стрептококковой ангиной и другими инфекциями. В обзоре критически проанализированы современные методы лабораторной диагностики ИМ с особым акцентом на полимеразную цепную реакцию (ПЦР) в различных модификациях. Рассмотрены принципы молекулярной диагностики, оптимальные матрицы для анализа, интерпретация количественных показателей вирусной нагрузки и возрастные особенности применения метода в педиатрической практике. Представлены данные сравнительной эффективности ПЦР, серологических тестов и методов прямого обнаружения вируса. Обсуждаются перспективные направления, включая цифровую ПЦР и next-generation sequencing (NGS) в диагностике ВЭБ-ассоциированных заболеваний. Обзор базируется на анализе современных международных руководств и мета-анализов последних лет.

инфекционный мононуклеозвирус Эпштейна-Баррполимеразная цепная реакциямолекулярная диагностикавирусная нагрузкапедиатриядифференциальная диагностикагерпесвирусные инфекциицифровая ПЦРлатентная инфекция.

References1

Luzuriaga K., Sullivan J.L. Infectious mononucleosis. N. Engl. J. Med. 2010;362(21):1993-2000. doi: 10.1056/NEJMcp1001116

Filatov N.F. Lymphadenosis acuta. Vestn. Oftalmol. 1887;4:417-424. (In Russ.)

Epstein M.A., Achong B.G., Barr Y.M. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet. 1964;1(7335):702-703. doi: 10.1016/s0140-6736(64)91524-7

Cohen J.I. Epstein-Barr virus infection. N. Engl. J. Med. 2000;343(7):481-492. doi: 10.1056/NEJM200008173430707

Young L.S., Yap L.F., Murray P.G. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat. Rev. Cancer. 2016;16(12):789-802. doi: 10.1038/nrc.2016.92

Dunmire S.K., Hogquist K.A., Balfour H.H. Infectious mononucleosis. Curr. Top. Microbiol. Immunol. 2015;390:211-240. doi: 10.1007/978-3-319-22822-8_9

Balfour H.H. Jr., Sifakis F., Sliman J.A. et al. Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States. J. Infect. Dis. 2013;208(8):1286-1293. doi: 10.1093/infdis/jit321

Centers for Disease Control and Prevention (CDC). Epstein-Barr Virus and Infectious Mononucleosis. Available at: https://www.cdc.gov/epstein-barr/index.html (accessed 15.01.2025).

Shannon-Lowe C., Rickinson A. The global landscape of EBV-associated tumors. Front. Oncol. 2019;9:713. doi: 10.3389/fonc.2019.00713

Pender M.P. CD8+ T-cell deficiency, Epstein-Barr virus infection, vitamin D deficiency, and steps to autoimmunity: a unifying hypothesis. Autoimmune Dis. 2012;2012:189096. doi: 10.1155/2012/189096

Jenson H.B. Epstein-Barr virus. Pediatr. Rev. 2011;32(9):375-383. doi: 10.1542/pir.32-9-375

Rea T.D., Russo J.E., Katon W. et al. Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J. Am. Board Fam. Pract. 2001;14(4):234-242.

Hadinoto V., Shapiro M., Sun C.C. et al. The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output. PLoS Pathog. 2009;5(7):e1000496. doi: 10.1371/journal.ppat.1000496

Tanner J., Weis J., Fearon D. et al. Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell. 1987;50(2):203-213. doi: 10.1016/0092-8674(87)90206-3

Thorley-Lawson D.A., Gross A. Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N. Engl. J. Med. 2004;350(13):1328-1337. doi: 10.1056/NEJMra032015

Hislop A.D., Taylor G.S., Sauce D., Rickinson A.B. Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu. Rev. Immunol. 2007;25:587-617. doi: 10.1146/annurev.immunol.25.022106.141553

Flano E., Kim I., Woodland D., Blackman M. Gamma-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells. J. Exp. Med. 2002;196(10):1363-1372. doi: 10.1084/jem.20020042

Babcock G.J., Decker L.L., Volk M., Thorley-Lawson D.A. EBV persistence in memory B cells in vivo. Immunity. 1998;9(3):395-404. doi: 10.1016/s1074-7613(00)80622-6

Carter J.W., Edlich R.F. Infectious mononucleosis in adolescence. J. Emerg. Med. 1985;3(5):321-326. doi: 10.1016/0736-4679(85)90005-3

Schumacher H.R., Borenstein M., Chernoff R. Atypical lymphocytes in toxic reactions. Am. J. Clin. Pathol. 1970;54(4):574-578. doi: 10.1093/ajcp/54.4.574

de-The G., Day N.E., Geser A. et al. Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study. IARC Sci. Publ. 1975;(11):3-16.

Henle G., Henle W., Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc. Natl. Acad. Sci. USA. 1968;59(1):94-101. doi: 10.1073/pnas.59.1.94

Horwitz C.A., Henle W., Henle G. et al. Clinical and laboratory evaluation of elderly patients with heterophil-antibody positive infectious mononucleosis. Am. J. Med. 1976;61(3):333-339. doi: 10.1016/0002-9343(76)90338-0

Sumaya C.V., Ench Y. Epstein-Barr virus infectious mononucleosis in children. I. Clinical and general laboratory findings. Pediatrics. 1985;75(6):1003-1010.

Gärtner B., Preiksaitis J.K. EBV viral load detection in clinical virology. J. Clin. Virol. 2010;48(2):82-90. doi: 10.1016/j.jcv.2010.03.016

Gerber P., Walsh J.H., Rosenblum E.N., Purcell R.H. Association of EB-virus infection with the post-perfusion syndrome. N. Engl. J. Med. 1969;281(12):665-669. doi: 10.1056/NEJM196909182811203

Pattengale P.K., Smith R.W., Gerber P. Selective transformation of B lymphocytes by EB virus. Lancet. 1974;2(7889):962-963. doi: 10.1016/s0140-6736(74)92093-2

Gulley M.L., Tang W. Laboratory assays for Epstein-Barr virus-related disease. J. Mol. Diagn. 2008;10(4):279-292. doi: 10.2353/jmoldx.2008.080023

Tsai D.E., Douglas L., Andreadis C. et al. EBV PCR in the diagnosis and monitoring of posttransplant lymphoproliferative disorder: results of a two-arm prospective trial. Am. J. Transplant. 2008;8(5):1016-1024. doi: 10.1111/j.1600-6143.2008.02183.x

Kimura H., Morita M., Yabuta Y. et al. Quantitative analysis of Epstein-Barr virus load by using a real-time PCR assay. J. Clin. Microbiol. 1999;37(1):132-136. doi: 10.1128/JCM.37.1.132-136.1999

Stevens S.J., Pronk I., Middeldorp J.M. Toward standardization of Epstein-Barr virus DNA load monitoring: unfractionated whole blood as preferred clinical specimen. J. Clin. Microbiol. 2001;39(4):1211-1216. doi: 10.1128/JCM.39.4.1211-1216.2001

Fan H., Gulley M.L. Epstein-Barr viral load measurement as a marker of EBV-related disease. Mol. Diagn. 2001;6(4):279-289. doi: 10.1054/modi.2001.29768

Faulkner G.C., Krajewski A.S., Crawford D.H. The ins and outs of EBV infection. Trends Microbiol. 2000;8(4):185-189. doi: 10.1016/s0966-842x(00)01736-8

Shaukat S., Anis S., Ejaz A. et al. Neurological complications of infectious mononucleosis. J. Pak. Med. Assoc. 2012;62(3):238-240.

Gulley M.L. Molecular diagnosis of Epstein-Barr virus-related diseases. J. Mol. Diagn. 2001;3(1):1-10. doi: 10.1016/s1525-1578(10)60642-7

Ryan J.L., Shen Y.J., Morgan D.R. et al. Epstein-Barr virus quantitation by real-time PCR targeting multiple gene segments: a novel approach to screen for the virus in paraffin-embedded tissue and plasma. J. Mol. Diagn. 2004;6(4):378-385. doi: 10.1016/s1525-1578(10)60522-7

Tierney R.J., Steven N., Young L.S., Rickinson A.B. Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J. Virol. 1994;68(11):7374-7385. doi: 10.1128/JVI.68.11.7374-7385.1994

Heid C.A., Stevens J., Livak K.J., Williams P.M. Real time quantitative PCR. Genome Res. 1996;6(10):986-994. doi: 10.1101/gr.6.10.986

Mackay I.M., Arden K.E., Nitsche A. Real-time PCR in virology. Nucleic Acids Res. 2002;30(6):1292-1305. doi: 10.1093/nar/30.6.1292

Kimura H., Ito Y., Suzuki R., Nishiyama Y. Measuring EBV load: the significance and application for each EBV-associated disease. Rev. Med. Virol. 2008;18(5):305-319. doi: 10.1002/rmv.582

Gärtner B., Preiksaitis J.K. EBV viral load detection in clinical virology. J. Clin. Virol. 2010;48(2):82-90. doi: 10.1016/j.jcv.2010.03.016

De Paschale M., Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World J. Virol. 2012;1(1):31-43. doi: 10.5501/wjv.v1.i1.31

Sumaya C.V., Ench Y. Epstein-Barr virus infectious mononucleosis in children. II. Heterophil antibody and viral-specific responses. Pediatrics. 1985;75(6):1011-1019.

Hjalgrim H., Askling J., Rostgaard K. et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N. Engl. J. Med. 2003;349(14):1324-1332. doi: 10.1056/NEJMoa023141

Nystad T.W., Myrmel H. Prevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG-, VCA IgM- and EBNA-1-antibodies and suspected infectious mononucleosis. J. Clin. Virol. 2007;38(4):292-297. doi: 10.1016/j.jcv.2006.12.013

Johannsen E.C., Schooley R.T., Kaye K.M. Epstein-Barr virus (infectious mononucleosis). In: Bennett J.E., Dolin R., Blaser M.J., eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Philadelphia: Elsevier; 2020:chap 139.

Rezk E., Nofal Y.H., Hamzeh A. et al. Steroids for symptom control in infectious mononucleosis. Cochrane Database Syst. Rev. 2015;(11):CD004402. doi: 10.1002/14651858.CD004402.pub3

Green M., Michaels M.G. Epstein-Barr virus infection and posttransplant lymphoproliferative disorder. Am. J. Transplant. 2013;13(Suppl 3):41-54. doi: 10.1111/ajt.12004

Kimura H. EBV-associated T/NK-cell lymphoproliferative diseases. In: Damania B., Kenney S.C., eds. Epstein-Barr Virus. Current Topics in Microbiology and Immunology. Vol. 390. Springer; 2015:299-324.

Wang W.J., Liu Y.L., Jiang Z. et al. The Viral Load of Epstein-Barr Virus in Blood of Children after Hematopoietic Stem Cell Transplantation. Biomed. Environ. Sci. 2022;35(9):804-810. doi: 10.3967/bes2022.052

van Esser J.W., van der Holt B., Meijer E. et al. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell--depleted SCT. Blood. 2001;98(4):972-978. doi: 10.1182/blood.v98.4.972

Stevens S.J., Verschuuren E.A., Pronk I. et al. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood. 2001;97(5):1165-1171. doi: 10.1182/blood.v97.5.1165

Putukian M., O'Connor F.G., Stricker P. et al. Mononucleosis and athletic participation: an evidence-based subject review. Clin. J. Sport Med. 2008;18(4):309-316. doi: 10.1097/JSM.0b013e31817e34e7

Barozzi P., Potenza L., Riva G. et al. B cells and herpesviruses: a model of lymphoproliferation. Autoimmun. Rev. 2007;7(2):132-136. doi: 10.1016/j.autrev.2007.02.018

Kawa K. Epstein-Barr virus-associated diseases in humans. Int. J. Hematol. 2000;71(2):108-117.

Hurt C., Tammaro D. Diagnostic evaluation of mononucleosis-like illnesses. Am. J. Med. 2007;120(10):911.e1-911.e8. doi: 10.1016/j.amjmed.2007.04.022

Rota P.A., Brown D.A. Update on the global distribution of genotypes of wild type measles viruses. J. Infect. Dis. 2004;189(Suppl 1):S27-S31. doi: 10.1086/377694

Ljungman P., Singh N. Human herpesvirus-6 infection in solid organ and stem cell transplant recipients. J. Clin. Virol. 2006;37(Suppl 1):S87-S91. doi: 10.1016/s1386-6532(06)70017-1

Caserta M.T., Hall C.B., Schnabel K. et al. Neuroinvasion and persistence of human herpesvirus 6 in children. J. Infect. Dis. 1994;170(6):1586-1589. doi: 10.1093/infdis/170.6.1586

Rector A., Lemey P., Laffut W. et al. Multi-modal molecular epidemiology of an atypical outbreak of Epstein-Barr virus infection. J. Clin. Virol. 2004;31(4):309-318. doi: 10.1016/j.jcv.2004.06.005

Hindson B.J., Ness K.D., Masquelier D.A. et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal. Chem. 2011;83(22):8604-8610. doi: 10.1021/ac202028g

Sanders R., Huggett J.F., Bushell C.A. et al. Evaluation of digital PCR for absolute DNA quantification. Anal. Chem. 2011;83(17):6474-6484. doi: 10.1021/ac103230c

Kwok H., Wu R.D., Sham P.C. et al. Genomic integrity and copy number of Epstein-Barr virus are maintained in Burkitt's lymphoma cells during serial xenografting. J. Virol. 2012;86(19):10707-10710. doi: 10.1128/JVI.01395-12

Mori Y., Notomi T. Loop-mediated isothermal amplification (LAMP): a rapid, accurate, and cost-effective diagnostic method for infectious diseases. J. Infect. Chemother. 2009;15(2):62-69. doi: 10.1007/s10156-009-0669-9

Poritz M.A., Blaschke A.J., Byington C.L. et al. FilmArray, an automated nested multiplex PCR system for multi-pathogen detection: development and application to respiratory tract infection. PLoS One. 2011;6(10):e26047. doi: 10.1371/journal.pone.0026047

Li Y., Li X., Zhang Y. et al. Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity. BMC Pediatr. 2025;25:98. doi: 10.1186/s12887-025-04642-3

Zhang H., Chen L., Wang X. et al. Retrospective Review of Children Hospitalized for Epstein-Barr Virus-Related Infectious Mononucleosis. Pediatr. Rep. 2025;17(3):457-472. doi: 10.3390/pediatric17030038

Chen J., Li M., Zhang Y. et al. MB based RT-qPCR increase the clinical application of cfEBV DNA for NPC in non-endemic area of China. Sci. Rep. 2025;15:93406. doi: 10.1038/s41598-025-93406-6

Balfour H.H. Jr., Holman C.J., Hokanson K.M. et al. A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J. Infect. Dis. 2005;192(9):1505-1512. doi: 10.1086/491740

Bauer C.C., Aberle S.W., Popow-Kraupp T. et al. Serum Epstein-Barr virus DNA load in primary Epstein-Barr virus infection. J. Med. Virol. 2005;75(1):54-58. doi: 10.1002/jmv.20229

Leong H.N., Tuke P.W., Tedder R.S. et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J. Med. Virol. 2007;79(1):45-51. doi: 10.1002/jmv.20760

Hjalgrim H., Friborg J., Melbye M. The epidemiology of EBV and its association with malignant disease. In: Arvin A., Campadelli-Fiume G., Mocarski E., et al., eds. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007:chap 52.

Palser A.L., Grayson N.E., White R.E. et al. Genome diversity of Epstein-Barr virus type 1 from EBV-associated diseases and healthy carriers. J. Virol. 2015;89(15):7912-7926. doi: 10.1128/JVI.00112-15

Rickinson A.B., Long H.M., Palendira U. et al. Cellular immune controls over Epstein-Barr virus infection: new lessons from the clinic. Curr. Opin. Immunol. 2014;26:22-27. doi: 10.1016/j.coi.2013.10.007

Cohen J.I., Kimura H., Nakamura S. et al. Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting. Ann. Oncol. 2009;20(5):824-830. doi: 10.1093/annonc/mdn583

Odumade O.A., Hogquist K.A., Balfour H.H. Jr. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin. Microbiol. Rev. 2011;24(1):193-209. doi: 10.1128/CMR.00044-10

Taylor G.S., Long H.M., Brooks J.M. et al. The immunology of EBV-induced lymphoma. Curr. Opin. Immunol. 2015;33:129-137. doi: 10.1016/j.coi.2015.03.001

Smets F., Sokal E.M. Epstein-Barr virus-related lymphoproliferation in children after liver transplant: role of immunity, diagnosis, and management. Pediatr. Transplant. 2002;6(4):280-287. doi: 10.1034/j.1399-3046.2002.01053.x

Kenagy D.N., Schlesinger Y.R., Weck K.E. et al. Epstein-Barr virus DNA in peripheral blood leukocytes of patients with posttransplant lymphoproliferative disease. Transplantation. 1995;60(6):547-554. doi: 10.1097/00007890-199509270-00001

Rowe D.T., Qu L., Reyes J. et al. Use of quantitative competitive PCR to measure Epstein-Barr virus genome load in the peripheral blood of pediatric transplant patients with lymphoproliferative disorders. J. Clin. Microbiol. 1997;35(6):1612-1615. doi: 10.1128/JCM.35.6.1612-1615.1997

The authors declare that there are no conflicts of interest present.