Epstein–Barr virus and related pathological processes. Part 1. Epidemiological and etiopathogenetic aspects of Epstein–Barr virus-associated infection
https://doi.org/10.22328/2077-9828-2026-18-1-24-36
Abstract
This analytical review consists of two interconnected parts devoted to human herpesvirus type 4, or Epstein–Barr virus (HHV-4, EBV). The first part examines the characteristics of the epidemic process and spread of EBV infection, the cytomorphological characteristics of the viral particle, and aspects of the etiopathogenesis of EBV-associated diseases in humans. Particular attention is paid to the unique molecular genetic stages and forms of EBV, risk factors that increase susceptibility to the pathogen, and conditions that promote viral reactivation. The presented data demonstrate a complex interaction between the pathogen and the human immune system, including mechanisms that facilitate lifelong persistence of the virus in the body.
About the Authors
D. D. Kruglova
St. Petersburg Pasteur Institute; City Polyclinic No. 17
Russian Federation
Russian Federation
A. M. Klementyev
AIDS Center of the Leningrad region
Russian Federation
Russian Federation
E. V. Zagalskaya
St. Petersburg Pasteur Institute 2S. S. Burdaeva; Pavlov First St. Petersburg State Medical University
Russian Federation
Russian Federation
S. S. Burdaeva
Pavlov First St. Petersburg State Medical University
Russian Federation
Russian Federation
V. V. Rassokhin
St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University
Russian Federation
Russian Federation
References
1. De Martel C., Ferlay J., Franceschi S. et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis // The Lancet. Oncology. 2012. Vol. 13, No. 6. Р. 607–615. https://doi.org/10.1016/S1470-2045(12)70137-7.
2. Yu H., Robertson E.S. Epstein–Barr Virus History and Pathogenesis // Viruses. 2023. Vol. 15, No. 3. Р. 714. https://doi.org/10.3390/v15030714.
3. Morawiec N., Adamczyk B., Spyra A. et al. The Role of Epstein–Barr Virus in the Pathogenesis of Autoimmune Diseases // Medicina. 2025. Vol. 61, No. 7. Р. 1148. https://doi.org/10.3390/medicina61071148.
4. Houen G., Trier N.H. Epstein–Barr Virus and Systemic Autoimmune Diseases // Frontiers in immunology. 2012. Vol. 11. Р. 587380. https://doi.org/10.3389/fimmu.2020.587380.
5. Filatova G.A., Khlanta D.A., Grishina T.I. et al. Clinical laboratory diagnosis of pathology associated with the Epstein–Barr virus: current status and prospects (review of literature). Сlinical laboratory diagnosis, 2023, Vol. 68, No. 5, рр. 280–284 (In Russ.). https://doi.org/10.51620/0869-2084-2023-68-5-280-284.
6. Sizova E.N., Fedorovskaya N.S. Evaluation of the Epstein–Barr virus occurrence at the pres ent stage (literature review). Hygiene and Sanitation, 2024, Vol. 103, No. 3, рр. 242–245 (In Russ.). https://doi.org/10.47470/0016-9900-2024-103-3-242-245. EDN: ldlpwd.
7. Solomay T.V., Voronin E.M., Semenenko T.A. et al. The Economic Burden of Epstein–Barr Virus Infection in the Russian Federation. Public Health and Life Environment — PH&LE, 2024, Vol. 32, No. 3, рр. 7–14 (In Russ.). https://doi.org/10.35627/2219-5238/2024-32-3-7-14.
8. Chinna P., Bratl K., Lambarey H. et al. The Impact of Co-Infections for Human Gammaherpesvirus Infection and Associated Pathologies // Int. J. Mol. Sci. 2023. Aug 22; Vol. 24, No. 17. Р. 13066. doi: 10.3390/ijms241713066.
9. Shilovsky B.V. et al. Regional differences in Epstein–Barr virus infection rates across Russia // Microbial Ecology in Health and Disease. 2023. Vol. 34, No. 1. Р. 1–10.
10. Nikolskiy M.A., Lioznov D.A., Malyavin A.G. Chronic EBV infection in clinical practice: what should be considered when diagnosing. Therapy, 2023, Vol. 2, рр. 56–61 (In Russ.). doi 10.18565/therapy.2023.2.56-61. EDN TCKAKZ.
11. Sergeeva N.S., Marshutina N.V., Solokhina M.P. et al. Epstein–Barr virus-associated solid malignancies. P. A. Herzen Journal of Oncology, 2018, Vol. 7, No. 5, рр. 80–89 (In Russ.). https://doi.org/10.17116/onkolog2018705180.
12. Iheukwumere I.H., Iheukwumere C.M., Unaeze B.C. et al. Epstein–Barr Virus: Structure, Pathogenesis, Diagnosis, and Management of Associated Diseases // IPS Journal of Basic and Clinical Medicine, 2023. Vol. 2, No. 4. Р. 133–142. https://doi.org/10.54117/ijbcm.v2i4.23.
13. Young L.S., Rickinson A.B. Epstein–Barr virus: 40 years on. Nature reviews // Cancer. 2004. Vol. 4, No. 10. Р. 757–768. https://doi.org/10.1038/nrc1452.
14. Avgil M., Ornoy A. Herpes simplex virus and Epstein–Barr virus infections in pregnancy: consequences of neonatal or intrauterine infection // Reproductive toxicology (Elmsford, N.Y.). 2006. Vol. 21, No. 4. Р. 436–445. https://doi.org/10.1016/j.reprotox.2004.11.014.
15. Sathiyamoorthy K., Jiang J., Hu Y.X. et al. Assembly and architecture of the EBV B cell entry triggering complex // PLoS pathogens. 2014. Vol. 10, No. 8. e1004309. https://doi.org/10.1371/journal.ppat.1004309.
16. Solares S., León J., García-Gutiérrez L. The Functional Interaction Between Epstein–Barr Virus and MYC in the Pathogenesis of Burkitt Lymphoma // Cancers. 2024. Vol. 16, No. 24. Р. 4212. https://doi.org/10.3390/cancers16244212.
17. Popkova M.I., Utkin O.V. Genetic diversity of the Epstein–Barr virus: a modern view of the problem. Journal of microbiology, epidemiology and immunobiology, 2022, Vol. 99, Nо. 1, рр. 93–108 (In Russ.). doi: 10.36233/0372-9311-228.
18. Bu G.L., Xie C., Kang Y.F. et al. How EBV Infects: The Tropism and Underlying Molecular Mechanism for Viral Infection // Viruses. 2022. Vol. 14, No. 11. Р. 2372. https://doi.org/10.3390/v14112372.
19. Crawford D.H. Biology and disease associations of Epstein–Barr virus // Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2001. Vol. 356, No. 1408. Р. 461–473. https://doi.org/10.1098/rstb.2000.0783.
20. Yu H., Robertson E.S. Epstein–Barr Virus History and Pathogenesis // Viruses. 2023. Vol. 15, No. 3. Р. 714. https://doi.org/10.3390/v15030714.
21. Nazarov E.U., Khodjaeva A.Sh., Khegay T.R. Epstein Barr virus: the results of half a century of research, but more questions than answers. Journal of Theoretical and Clinical Medicine, 2018, No. 2, рр. 118–124 (In Russ.). EDN HLQVMF.
22. Fugl A., Andersen C.L. Epstein–Barr virus and its association with disease — a review of relevance to general practice // BMC family practice. 2019. Vol. 20, No. 1. Р. 62. https://doi.org/10.1186/s12875-019-0954-3.
23. Damania B., Kenney S.C., Raab-Traub N. Epstein–Barr virus: Biology and clinical disease // Cell. 2022. Vol. 185, No. 20. Р. 3652–3670. https://doi.org/10.1016/j.cell.2022.08.026.
24. Huang W., Bai L., Tang H. Epstein–Barr virus infection: the micro and macro worlds // Virology journal. 2023. Vol. 20, No. 1. Р. 220. https://doi.org/10.1186/s12985-023-02187-9.
25. Sun Y., Ling S., Tang D. et al. Advances in Epstein–Barr Virus Detection: From Traditional Methods to Modern Technologies // Viruses. 2025. Vol. 17, No. 8. Р. 1026. https://doi.org/10.3390/v17081026.
26. Frappier L. Epstein–Barr virus: Current questions and challenges // Tumour virus research. 2021. Vol. 12. Р. 200218. https://doi.org/10.1016/j.tvr.2021.200218.
27. Ma S.D., Hegde S., Young K.H. et al. A new model of Epstein–Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas // Journal of virology. 2011. Vol. 85, No. 1. Р. 165–177. https://doi.org/10.1128/JVI.01512-10.
28. Ma Z., Damania B. The cGAS-STING Defense Pathway and Its Counteraction by Viruses // Cell host microbe. 2016. Vol. 19, No. 2. Р. 150– 158. https://doi.org/10.1016/j.chom.2016.01.010
29. Wyżewski Z., Mielcarska M.B., Gregorczyk-Zboroch K.P., Myszka A. Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives // International journal of molecular sciences. 2022. Vol. 23, No. 13. Р. 7265. https://doi.org/10.3390/ijms23137265.
30. Silva J.M., Alves C.E.C., Pontes G.S. Epstein–Barr virus: the mastermind of immune chaos // Frontiers in immunology. 2024. Vol. 15. Р. 1297994. https://doi.org/10.3389/fimmu.2024.1297994.
31. Jog N.R., Chakravarty E.F., Guthridge J.M., James J.A. Epstein Barr Virus Interleukin 10 Suppresses Anti-inflammatory Phenotype in Human Monocytes // Frontiers in immunology. 2018. Vol. 9. Р. 2198. https://doi.org/10.3389/fimmu.2018.02198.
32. Jochum S., Moosmann A., Lang S., Hammerschmidt W., Zeidler R. The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from immune recognition and elimination // PLoS pathogens. 2012. Vol. 8, No. 5. e1002704. https://doi.org/10.1371/journal.ppat.1002704.
33. Rowe M., Glaunsinger B., van Leeuwen D. et al. Host shutoff during productive Epstein–Barr virus infection is mediated by BGLF5 and may con tribute to immune evasion // Proceedings of the National Academy of Sciences of the United States of America. 2007. Vol. 104, No. 9. Р. 3366–3371. https://doi.org/10.1073/pnas.0611128104.
34. Kuznetsov S.A., Alekseeva E.V. Genetic predisposition to severe forms of Epstein–Barr virus disease // Genetics and Molecular Biology. 2025. Vol. 48, No. 2. Р. 234–242.
35. Smatti M.K., Al-Sadeq D.W., Ali N.H. et al. Epstein–Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update // Front. Oncol. 2018. Jun 13; Vol. 8. Р. 211. doi: 10.3389/fonc.2018.00211. PMID: 29951372; PMCID: PMC6008310.
36. Kawada J.I., Ito Y., Oshima K. et al.; Committee for the Development of Recommendations for the Treatment of Chronic Active Epstein–Barr virus Disease, and related diseases (research group of the Ministry of Health, Labor and Welfare of Japan). Updated recommendations for the treatment of the chronic active form of the disease caused by the Epstein–Barr virus // Int. J. Hematol. 2023 Nov; Vol. 118, No. 5. Р. 568–576. doi: 10.1007/s12185-023-03660-5. Epub 2023 Sep 20. PMID: 37728704; PMCID: PMC10615970.
37. Indari O., Ghosh S., Bal A.S. et al. Awakening the sleeping giant: Epstein–Barr virus reactivation by biological agents // Pathogens and disease. 2024. Vol. 82, ftae002. https://doi.org/10.1093/femspd/ftae002.
38. Solomay T.V., Semenenko T.A., Tutelyan A.V., Bobrova M.V. Epidemiological characteristics of Epstein–Barr virus infection. Journal of microbiology, epidemiology and immunobiology, 2021, Vol. 98, Nо. 6, рр. 685–696 (In Russ.). doi: 10.36233/0372-9311-139.
39. Boeva E.V., Rassokhin V.V., Norka A.O., Knizhnikova A.A., Korobova Z.R., Arsent’yeva N.A., Ivanova A.R., Klementev А.M., Belyakov N.A. Editorial article based on the results of the study human herpes virus reactivation in the pathogenesis of long COVID. HIV Infection and Immunosuppressive Disorders. 2025. Vol. 17, No. 2, рр. 7–23 (In Russ.). https://doi.org/10.22328/2077-9828-2025-17-2-7-23.
40. Anderson A.G., Gaffy C.B., Weseli J.R., Gorres K.L. Inhibition of Epstein–Barr Virus Lytic Reactivation by the Atypical Antipsychotic Drug Clozapine // Viruses. 2019. Vol. 11, No. 5. Р. 450. https://doi.org/10.3390/v11050450.
41. Tohyama M., Hashimoto K., Oda F. et al. Influence of corticosteroid therapy on viral reactivation in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms // J. Dermatol. 2020. Vol. 47. Р. 476–482. https://doi.org/10.1111/1346-8138.15294
42. Chen Y., Chang E.T., Liu Q. et al. Environmental Factors for Epstein–Barr Virus Reactivation in a High-Risk Area of Nasopharyngeal Carcinoma: A Population-Based Study // Open forum infectious diseases. 2022. Vol. 9, No. 5. Р. ofac128. https://doi.org/10.1093/ofid/ofac128.
43. Zhao L., Xie F., Wang T.T. et al. Chlorpyrifos Induces the Expression of the Epstein–Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species // Oxidative medicine and cellular longevity, 2015. Vol. 309125. https://doi.org/10.1155/2015/309125.
44. Zhu P., Chen Y.J., Hao J.H. et al. Maternal depressive symptoms related to Epstein–Barr virus reactivation in late pregnancy // Sci Rep. 2013. Vol. 3. Р. 3096. https://doi.org/10.1038/srep03096.
45. Shafiee A., Nakhaee Z., Amini M.J. et al. Bidirectional relationship between human herpes virus reactivation and depression: a systematic review and meta-analysis // Journal of neurovirology. 2025. Vol. 31, No. 2. Р. 145–153. https://doi.org/10.1007/s13365-025-01246-x.
46. Romanenko Y.F. et al. Occupational risks associated with Epstein–Barr virus exposure // Occupational Health Quarterly. 2024. Vol. 39, No. 2. Р. 56–62.
47. Sergeev A.A. et al. Chronic complications following Epstein–Barr virus infection in elderly individuals // Gerontology Research. 2022. Vol. 34, No. 6. Р. 432–439.
48. Kaira A.N., Solomai T.V., Semenenko T.A. Epidemiology and prevention of Epstein–Barr virus infection. Moscow: Federal State Budgetary Educational Institution of Continuing Professional Education «Russian Medical Academy of Continuous Professional Education» of the Ministry of Health of the Russian Federation 2022. 81 p. (In Russ.). ISBN 978-5-7249-3249-3. EDN YZNWEG.
49. Kim H.J. et al. Environmental influences on Epstein–Barr virus activity // Global Change Biology. 2021. Vol. 27, No. 12. Р. 4567–4578.
50. Zhao Y., Zhang Q., Zhang B. et al. Epstein–Barr Viruses: Their Immune Evasion Strategies and Implications for Autoimmune Diseases // Int. J. Mol. Sci. 2024. Jul 26; Vol. 25, No. 15. Р. 8160. doi: 10.3390/ijms25158160. PMID: 39125729; PMCID: PMC11311853.
51. Albanese M., Tagawa T., Hammerschmidt W. Strategies of Epstein–Barr virus to evade innate antiviral immunity of its human host // Front. Microbiol. 2022. Vol. 13. Р. 955603. doi: 10.3389/fmicb.2022.955603.
52. Mazus A.I., Tsyganova E.V., Glukhoedova N.V., Zhilenkova A.S. Epstein–Barr virus infection: from infectious mononucleosis to lymphoproliferative disorder. Therapy, 2021, No. 2, рр. 112–122 (In Russ.). https://dx.doi.org/10.18565/therapy.2021.2.112-122.
53. Chijioke O., Landtwing V., Münz C. NK Cell Influence on the Outcome of Primary Epstein–Barr Virus Infection // Front. Immunol. 2016. Vol. 7. Р. 323. doi: 10.3389/fimmu.2016.00323.
54. Shindiapina P., Ahmed E.H., Mozhenkova A. еt al. Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals // Front. Oncol. 2020. Vol. 10. Р. 1723. doi: 10.3389/fonc.2020.01723.
55. Puzyreva L.V., Safonov A.D. Infections caused by Epstein–Barr virus in HIV-infected patients. Journal of Microbiology, Epidemiology and Immunobiology, 2016, No. 6, pp. 108–116 (In Russ.)
56.
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For citations:
Kruglova D.D., Klementyev A.M., Zagalskaya E.V., Burdaeva S.S., Rassokhin V.V. Epstein–Barr virus and related pathological processes. Part 1. Epidemiological and etiopathogenetic aspects of Epstein–Barr virus-associated infection. HIV Infection and Immunosuppressive Disorders. 2026;18(1):24-36. (In Russ.) https://doi.org/10.22328/2077-9828-2026-18-1-24-36
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