EPSTEIN-BARR VIRUS: CAUSES, CONSEQUENCES, DIAGNOSIS AND TREATMENT OF EPSTEIN-BARR VIRUS IN HUMAN

  • Marko Koprivica 1. University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia; 2. Institute of Public Health of Vojvodina, Novi Sad, Serbia
Keywords: Epstein-Barr virus, carcinogenesis, transplantation, serological methods, autoimmune reactions

Abstract


The Epstein-Barr virus (EBV) belongs to the family of herpesviruses, subfamily Gammaherpesvirinae, and genus Lymphocryptovirus. Despite this classification, there are two serotypes of the Epstein-Barr virus, namely type A and type B. Both types play significant roles in the development of viremia. Additionally, EBV infection can lead to lymphadenopathy, upper respiratory tract obstruction, spleen rupture, thrombocytopenia, and recently, there has been increased emphasis on the connection between this virus and certain malignant neoplasms. Diagnosing this virus can be challenging if clinicians rely solely on serological confirmation. In some cases, it is necessary to perform more specific methods, in addition to considering the clinical picture and history, to prove the presence of the virus in blood, nasopharyngeal swabs, and other tissue samples. The aim of this paper is to present the severity and consequences caused by the Epstein-Barr virus and to emphasize the importance of preventive measures in preventing the virus from coming into contact with susceptible individuals. Prevention plays a crucial role in reducing contact with the virus. Since the infection spreads via droplets, wearing masks in healthcare facilities and regular hand washing are hygiene priorities to prevent infection and further transmission.

References

Houen G, Trier NH. Epstein-Barr virus and systemic autoimmune diseases. Front Immunol. 2021;11:587380. doi:10.3389/fimmu.2020.587380.

Soldan SS, Lieberman PM. Epstein-Barr virus and multiple sclerosis. Nat Rev Microbiol. 2023;21(1):51-64. doi: 10.1038/s41579-022-00770-5.

Sausen DG, Bhutta MS, Gallo ES, Dahari H, Borenstein R. Stress-induced Epstein-Barr virus reactivation. Biomolecules.2021;11(9):1380. doi:10.3390/biom11091380.

Zhang N, Zuo Y, Jiang L, Peng Y, Huang X, Zuo L. Epstein-Barr virus and neurological diseases. Front Mol Biosci. 2022;8:816098. doi:10.3389/fmolb.2021.816098.

Cui X, Snapper CM. Epstein Barr virus: development of vaccines and immune cell therapy for EBV-associated diseases. Front Immunol. 2021;12:734471. doi:10.3389/fimmu.2021.734471.

Guo R, Gewurz BE. Epigenetic control of the Epstein-Barr lifecycle. Curr Opin Virol. 2022;52:78-88. doi:10.1016/j.coviro.2021.11.013.

Wong Y, Meehan MT, Burrows SR, Doolan DL, Miles JJ. Estimating the global burden of Epstein-Barr virus-related cancers. J Cancer Res Clin Oncol. 2022;148(1):31-46. doi:10.1007/s00432-021-03824-y.

Cantù G. Nasopharyngeal carcinoma. A "different" head and neck tumour. Part A: from histology to staging. Acta Otorhinolaryngol Ital. 2023;43(2):85-98. doi:10.14639/0392-100X-N2222.

Murata T, Sugimoto A, Inagaki T, Yanagi Y, Watanabe T, Sato Y, et al. Molecular basis of Epstein-Barr virus latency establishment and lytic reactivation. Viruses. 2021;13(12):2344. doi:10.3390/v13122344.

Fevang B, Wyller VBB, Mollnes TE, Pedersen M, Asprusten TT, Michelsen A, et al. Lasting immunological imprint of primary Epstein-Barr virus infection with associations to chronic low-grade inflammation and fatigue. Front Immunol. 2021;12:715102. doi:10.3389/fimmu.2021.715102.

Xu X, Fan Z, Wang Y, Huang F, Xu Y, Sun J, et al. Effect of sorafenib maintenance on Epstein-Barr virus and cytomegalovirus infections in patients with FLT3-ITD AML undergoing allogeneic hematopoietic stem cell transplantation: a secondary analysis of a randomized clinical trial. BMC Med. 2022;20(1):282.doi:10.1186/s12916-022-02479-x.

Lechner M, Schartinger VH, Steele CD, Nei WL, Ooft ML, Schreiber LM, et al. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. Nat Commun. 2021;12(1):117. doi:10.1038/s41467-020-20308-8.

Maulani C, Auerkari EI, C Masulili SL, Soeroso Y, Djoko Santoso W, S Kusdhany L. Association between Epstein-Barr virus and periodontitis: a meta-analysis. PLoS One. 2021;16(10):e0258109. doi:10.1371/journal.pone.0258109.

Miller JA, Sahoo MK, Yamamoto F, Huang C, Wang H, Zehnder JL, et al. Multiplex Epstein-Barr virus BALF2 genotyping detects high-risk variants in plasma for population screening of nasopharyngeal carcinoma. Mol Cancer. 2022;21(1):154. doi:10.1186/s12943-022-01625-6.

Abusalah MAH, Irekeola AA, Hanim Shueb R, Jarrar M, Yean Yean C. Prognostic Epstein-Barr Virus (EBV) miRNA biomarkers for survival outcome in EBV-associated epithelial malignancies: Systematic review and meta-analysis. PLoS One. 2022;17(4):e0266893. doi:10.1371/journal.pone.0266893.

Zhao CX, Wen JJ, Fu D, Xu PP, Cheng S, Wang L, et al. Clinical and molecular features of Epstein-Barr virus-positive diffuse large B-cell lymphoma: results in a multi-center trial. Clin Transl Med. 2021;11(9):e539. doi:10.1002/ctm2.539.

Duque X, Mendoza E, Morán S, Suárez-Arriaga MC, Morales-Sánchez A, Fontes-Lemus JI, eta al. Epstein–Barr virus infection is associated with elevated Hepcidin levels. Int J Mol Sci. 2023; 24(2):1630. doi: 10.3390/ijms24021630.

Lupo J, Truffot A, Andreani J, Habib M, Epaulard O, Morand P, et al. Virological markers in Epstein–Barr virus-associated diseases. Viruses. 2023; 15(3):656. doi: 10.3390/v15030656.

Palma-Lara I, Sánchez-Aldana AE, Jiménez-Hernández E, Martínez-Villegas O, Núñez-Enríquez JC, Mejía-Aranguré JM, et al. Variable expression of Notch1 and Pax5 in classical Hodgkin lymphoma and infection with Epstein–Barr in pediatric patients. Microorganisms. 2020; 8(6):958. doi: 10.3390/microorganisms8060958.

Bassil N, Rostaing L, Mengelle C, Kallab S, Esposito L, Guitard J, et al. Prospective monitoring of cytomegalovirus, Epstein-Barr virus, BK virus, and JC virus infections on belatacept therapy after a kidney transplant. Exp Clin Transplant. 2014;12(3):212-9.

Bajda S, Blazquez-Navarro A, Samans B, Wehler P, Kaliszczyk S, Amini L, et al. The role of soluble mediators in the clinical course of EBV infection and B cell homeostasis after kidney transplantation. Sci Rep. 2020;10(1):19594.doi:10.1038/s41598-020-76607-z.

Lupo J, Tsougaev M, Blachier S, Chovelon G, Truffot A, Leroy C, et al. Comparison of Elecsys and Liaison immunoassays to determine Epstein-Barr virus serological status using further diagnostic approaches to clarify discrepant results. J Med Virol. 2023;95(1):e28166. doi: 10.1002/jmv.28166.

Peeling RW, Heymann DL, Teo YY, Garcia PJ. Diagnostics for COVID-19: moving from pandemic response to control. Lancet. 2022;399(10326):757-68. doi:10.1016/S0140-6736(21)02346-1.

Ciotti M, Benedetti F, Zella D, Angeletti S, Ciccozzi M, Bernardini S. SARS-CoV-2 infection and the COVID-19 pandemic emergency: the importance of diagnostic methods. Chemotherapy. 2021;66(1-2):17-23. doi:10.1159/000515343.

Yang X, Goldstein AM, Chen CJ, Rabkin CS, Chen JY, Cheng YJ, et al. Distribution of Epstein-Barr viral load in serum of individuals from nasopharyngeal carcinoma high-risk families in Taiwan. Int J Cancer. 2006;118(3):780-4. doi:10.1002/ijc.21396.

Kroll JL, Beam C, Li S, Viscidi R, Dighero B, Cho A, et al. Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes. J Clin Virol. 2013;57(2):115-9. doi:10.1016/j.jcv.2013.01.016.

Hammad A, Coles A, Gibson MDJ. False positive mumps serology in a patient with cerebral systemic lupus erythematosus. Rheumatol Adv Pract. 2018;2(Suppl 1):rky033. doi: 10.1093/rap/rky033.

Miskovic R, Cirkovic A, Miljanovic D, Jeremic I, Grk M, Basaric M, et al. Epstein–Barr virus reactivation as a new predictor of achieving remission or lupus low disease activity state in patients with Systemic Lupus Erythematosus with cutaneous involvement. Int J Mol Sci. 2023; 24(7):6156. doi.10.3390/ijms24076156.

Qasem A, Shaw AM, Elkamel E, Naser SA. Coronavirus Disease 2019 (COVID-19) diagnostic tools: a focus on detection technologies and limitations. Curr Issues Mol Biol. 2021;43(2):728-48. doi:10.3390/cimb43020053.

Kiiskinen SJ, Luomala O, Häkkinen T, Lukinmaa-Åberg S, Siitonen A. Evaluation of the serological point-of-care testing of infectious mononucleosis by data of external quality control samples. Microbiol Insights. 2020;13:1178636120977481. doi: 10.1177/1178636120977481.

Wojciechowska-Koszko I, Kwiatkowski P, Sienkiewicz M, Kowalczyk M, Kowalczyk E, Dołęgowska B. Cross-reactive results in serological tests for Borreliosis in patients with active viral infections. Pathogens. 2022; 11(2):203. doi: 10.3390/pathogens11020203.

Zubchenko S, Kril I, Potemkina H, Havrylyuk A, Kuzan A, Gamian A, et al. Low level of advanced glycation end products in serum of patients with allergic rhinitis and chronic Epstein-Barr virus infection at different stages of virus persistence. J Immunol Res. 2022;2022:4363927. doi: 10.1155/2022/4363927.

Rubinstein JD, Lutzko C, Leemhuis T, Zhu X, Pham G, Ray L, et al. Scheduled administration of virus-specific T cells for viral prophylaxis after pediatric allogeneic stem cell transplant. Blood Adv. 2022;6(9):2897-907. doi:10.1182/bloodadvances.2021006309.

Suzuki K, Namba K, Hase K, Mizuuchi K, Iwata D, Ito T, et al. A case of Epstein-Barr virus acute retinal necrosis successfully treated with foscarnet. Am J Ophthalmol Case Rep. 2022;25:101363. doi:10.1016/j.ajoc.2022.101363.

Ye Z, Chen L, Zhong H, Cao L, Fu P, Xu J. Epidemiology and clinical characteristics of Epstein-Barr virus infection among children in Shanghai, China, 2017-2022. Front Cell Infect Microbiol. 2023;13:1139068. doi:10.3389/fcimb.2023.1139068.

Medović R, Igrutinović Z, Radojević-Marjanović R, Marković S, Rasković Z, Simović A, et al. Clinical and laboratory differences between Epstein-Barr and cytomegalovirus infectious mononucleosis in children. Srp Arh Celok Lek. 2016;144(1-2):56-62. doi:10.2298/sarh1602056m.

Published
2024/02/27
Section
Review article