Epstein–Barr Virus in the Development of Colorectal Cancer (Review)

The study of the influence of the Epstein–Barr virus (EBV) on the development of colorectal cancer is of current interest, particularly in light of the active discussion of the participation of this virus in the carcinogenesis of stomach cancer. In this review, aimed at a fundamental understanding of the processes associated with the impact of EBV on the human body, attention is paid to the issues of the life cycle of the virus, its phases (latent and lytic), as well as proteins that may be detected in each of the phases. The papers reporting on the role of EBV in the development of colorectal cancer have been analyzed. A summary table indicating the population under study, the number of samples, the method, and the result obtained is provided. Given that the primary cells affected by EBV are lymphocytes, it is logical to assume the involvement of this virus in the development of inflammatory bowel diseases. The review cites studies which confirm the presence of virus DNA in tissues in the inflammatory diseases of the colon, including microscopic and ulcerative colitis. To confirm the direct impact of EBV on the development of colorectal cancer, large studies with applying various methods for detecting the virus and the mandatory description of its localization are required. Besides, it is necessary to correlate these data with the clinical and morphological characteristics of EBV.

1. Fernandes Q., Gupta I., Vranic S., Al Moustafa A.E. Human papillomaviruses and Epstein–Barr virus interactions in colorectal cancer: a brief review. Pathogens 2020; 9(4): 300, https://doi.org/10.3390/pathogens9040300.
2. Mui U.N., Haley C.T., Tyring S.K. Viral oncology: molecular biology and pathogenesis. J Clin Med 2017; 6(12): 111, https://doi.org/10.3390/jcm6120111.
3. Münz C. Latency and lytic replication in Epstein–Barr virus-associated oncogenesis. Nat Rev Microbiol 2019; 17(11): 691–700, https://doi.org/10.1038/s41579-019-0249-7.
4. Thompson M.P., Kurzrock R. Epstein–Barr virus and cancer. Clin Cancer Res 2004; 10(3): 803–821, https://doi.org/10.1158/1078-0432.ccr-0670-3.
5. Tsang C.M., Tsao S.W. The role of Epstein–Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Virol Sin 2015; 30(2): 107–121, https://doi.org/10.1007/s12250-015-3592-5.
6. Chen X.Z., Chen H., Castro F.A., Hu J.K., Brenner H. Epstein–Barr virus infection and gastric cancer: a systematic review. Medicine (Baltimore) 2015; 94(20): e792, https://doi.org/10.1097/md.0000000000000792.
7. Vedham V., Verma M., Mahabir S. Early-life exposures to infectious agents and later cancer development. Cancer Med 2015; 4(12): 1908–1922, https://doi.org/10.1002/cam4.538.
8. Cyprian F.S., Al-Farsi H.F., Vranic S., Akhtar S., Al     Moustafa     A.E. Epstein–Barr virus and human papillomaviruses interactions and their roles in the initiation of epithelial–mesenchymal transition and cancer progression. Front Oncol 2018; 8: 111, https://doi.org/10.3389/fonc.2018.00111.
9. Al-Thawadi H., Ghabreau L., Aboulkassim T., Yasmeen A., Vranic S., Batist G., Al Moustafa A.E. Co-incidence of Epstein–Barr virus and high-risk human papillomaviruses in cervical cancer of Syrian women. Front Oncol 2018; 8: 250, https://doi.org/10.3389/fonc.2018.00250.
10. She Y., Nong X., Zhang M., Wang M. Epstein–Barr virus infection and oral squamous cell carcinoma risk: a meta-analysis. PLoS One 2017; 12(10): e0186860, https://doi.org/10.1371/journal.pone.0186860.
11. Mozaffari H.R., Ramezani M., Janbakhsh A., Sadeghi M. Malignant salivary gland tumors and Epstein–Barr virus (EBV) infection: a systematic review and meta-analysis. Asian Pac J Cancer Prev 2017; 18(5): 1201–1206, https://doi.org/10.22034/apjcp.2017.18.5.1201.
12. Al Moustafa A.E., Al-Antary N., Aboulkassim T., Akil N., Batist G., Yasmeen A. Co-prevalence of Epstein–Barr virus and high-risk human papillomaviruses in Syrian women with breast cancer. Hum Vaccin Immunother 2016; 12(7): 1936–1939, https://doi.org/10.1080/21645515.2016.1139255.
13. Whitaker N.J., Glenn W.K., Sahrudin A., Orde M.M., Delprado W., Lawson J.S. Human papillomavirus and Epstein Barr virus in prostate cancer: koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer. Prostate 2013; 73(3): 236–241, https://doi.org/10.1002/pros.22562.
14. Shlyakhtunov E.A., Savchenok A.V. Breast cancer and the Epstein–Barr virus. Uspehi molekularnoj onkologii 2015; 2(4): 26–27.
15. Aran V., Victorino A.P., Thuler L.C., Ferreira C.G. Colorectal cancer: epidemiology, disease mechanisms and interventions to reduce onset and mortality. Clin Colorectal Cancer 2016; 15(3): 195–203, https://doi.org/10.1016/j.clcc.2016.02.008.
16. Marley A.R., Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet 2016; 7(3): 105–114.
17. Polyakova A.S., Bakradze M.D., Dzhivanshiryan G.V., Tatochenko V.K. Current view of the Epstein–Barr virus infection. Farmateka 2019; 26(10): 27–34, https://doi.org/10.18565/pharmateca.2019.10.27-34.
18. Murata T., Tsurumi T. Switching of EBV cycles between latent and lytic states. Rev Med Virol 2014; 24(3): 142–153, https://doi.org/10.1002/rmv.1780.
19. Rickinson A. Epstein–Barr virus. Virus Res 2002; 82(1–2): 109–113, https://doi.org/10.1016/s0168-1702(01)00436-1.
20. Skalsky R.L., Cullen B.R. EBV noncoding RNAs. Curr Top Microbiol Immunol 2015; 391: 181–217, https://doi.org/10.1007/978-3-319-22834-1_6.
21. Thorley-Lawson D.A. EBV persistence — introducing the virus. Curr Top Microbiol Immunol 2015; 390(Pt 1): 151–209, https://doi.org/10.1007/978-3-319-22822-8_8.
22. 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, https://doi.org/10.1038/nrc.2016.92.
23. Babcock G.J., Hochberg D., Thorley-Lawson A.D. The expression pattern of Epstein–Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 2000; 13(4): 497–506, https://doi.org/10.1016/s1074-7613(00)00049-2.
24. Hartung A., Makarewicz O., Egerer R., Karrasch M., Klink A., Sauerbrei A., Kentouche K., Pletz M.W. EBV miRNA expression profiles in different infection stages: a prospective cohort study. PLoS One 2019; 14(2): e0212027, https://doi.org/10.1371/journal.pone.0212027.
25. Kurth J., Spieker T., Wustrow J., Strickler G.J., Hansmann L.M., Rajewsky K., Küppers R. EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity 2000; 13(4): 485–495, https://doi.org/10.1016/s1074-7613(00)00048-0.
26. Hochberg D., Middeldorp J.M., Catalina M., Sullivan J.L., Luzuriaga K., Thorley-Lawson D.A. Demonstration of the Burkitt’s lymphoma Epstein–Barr virus phenotype in dividing latently infected memory cells in vivo. Proc Natl Acad Sci U S A 2004; 101(1): 239–244, https://doi.org/10.1073/pnas.2237267100.
27. Balfour H.H. Jr., Sifakis F., Sliman J.A., Knight J.A., Schmeling D.O., Thomas W. Age-specific prevalence of Epstein–Barr virus infection among individuals aged 6–19 years in the United States and factors affecting its acquisition. J Infect Dis 2013; 208(8): 1286–1293, https://doi.org/10.1093/infdis/jit321.
28. Tsurumi T., Fujita M., Kudoh A. Latent and lytic Epstein–Barr virus replication strategies. Rev Med Virol 2005; 15(1): 3–15, https://doi.org/10.1002/rmv.441.
29. Buettner M., Lang A., Tudor C.S., Meyer B., Cruchley A., Barros M.H.M., Farrell P.J., Jäck H.M., Schuh W., Niedobitek G. Lytic Epstein–Barr virus infection in epithelial cells but not in B-lymphocytes is dependent on Blimp1. J Gen Virol 2012; 93(Pt 5): 1059–1064, https://doi.org/10.1099/vir.0.038661-0.
30. Frappier L. Ebna1. Curr Top Microbiol Immunol 2015; 391: 3–34, https://doi.org/10.1007/978-3-319-22834-1_1.
31. Bedri S., Sultan A.A., Alkhalaf M., Al Moustafa A.E., Vranic S. Epstein–Barr virus (EBV) status in colorectal cancer: a mini review. Hum Vaccin Immunother 2019; 15(3): 603–610, https://doi.org/10.1080/21645515.2018.1543525.
32. Tsai C.Y., Liu Y.Y., Liu K.H., Hsu J.T., Chen T.C., Chiu C.T., Yeh T.S. Comprehensive profiling of virus microRNAs of Epstein–Barr virus-associated gastric carcinoma: highlighting the interactions of ebv-Bart9 and host tumor cells. J Gastroenterol Hepatol 2017; 32(1): 82–91, https://doi.org/10.1111/jgh.13432.
33. Ignatova E.O., Seryak D.A., Fedyanin M.Yu., Tryakin A.A., Pokataev I.A., Menshikova S.F., Vakhabova Yu.V., Karbyshev M.S., Smirnova K.V., Tulyandin S.A. Molecular portrait of stomach cancer associated with the Epstein–Barr virus. Uspehi molekularnoj onkologii 2020; 7(3): 27–36, https://doi.org/10.17650/2313-805x-2020-7-3-27-36.
34. Malki M.I., Gupta I., Fernandes Q., Aboulkassim T., Yasmeen A., Vranic S., Al Moustafa A.E., Al-Thawadi H.A. Co-presence of Epstein–Barr virus and high-risk human papillomaviruses in Syrian colorectal cancer samples. Hum Vaccin Immunother 2020; 16(10): 2403–2407, https://doi.org/10.1080/21645515.2020.1726680.
35. Gupta I., Al Farsi H., Jabeen A., Skenderi F., Al-Thawadi H., AlAhmad Y.M., Al Moustafa A.E., Vranic S. High-risk human papillomaviruses and Epstein–Barr virus in colorectal cancer and their association with clinicopathological status. Pathogens 2020; 9(6): 452, https://doi.org/10.3390/pathogens9060452.
36. Sarvari J., Mahmoudvand S., Pirbonyeh N., Safaei A., Hosseini S.Y. The very low frequency of Epstein–Barr JC and BK viruses DNA in colorectal cancer tissues in Shiraz, Southwest Iran. Pol J Microbiol 2018; 67(1): 73–79, https://doi.org/10.5604/01.3001.0011.6146.
37. Al-Antary N., Farghaly H., Aboulkassim T., Yasmeen A., Akil N., Al Moustafa A.E. Epstein–Barr virus and its association with Fascin expression in colorectal cancers in the Syrian population: a tissue microarray study. Hum Vaccin Immunother 2017; 13(7): 1573–1578, https://doi.org/10.1080/21645515.2017.1302046.
38. Mehrabani-Khasraghi S., Ameli M., Khalily F. Demonstration of herpes simplex virus, cytomegalovirus, and Epstein–Barr virus in colorectal cancer. Iran Biomed J 2016; 20(5): 302–306, https://doi.org/10.22045/ibj.2016.08.
39. Tafvizi F., Fard Z.T., Assareh R. Epstein–Barr virus DNA in colorectal carcinoma in Iranian patients. Pol J Pathol 2015; 66(2): 154–160, https://doi.org/10.5114/pjp.2015.53012.
40. Sole C.V., Calvo F.A., Ferrer C., Alvarez E., Carreras J.L., Ochoa E. Human cytomegalovirus and Epstein–Barr virus infection impact on 18F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy. Eur J Nucl Med Mol Imaging 2015; 42(2): 186–196, https://doi.org/10.1007/s00259-014-2910-8.
41. Guan X., Yi Y., Huang Y., Hu Y., Li X., Wang X., Fan H., Wang G., Wang D. Revealing potential molecular targets bridging colitis and colorectal cancer based on multidimensional integration strategy. Oncotarget 2015; 6(35): 37600–37612, https://doi.org/10.18632/oncotarget.6067.
42. Fiorina L., Ricotti M., Vanoli A., Luinetti O., Dallera E., Riboni R., Paolucci S., Brugnatelli S., Paulli M., Pedrazzoli P., Baldanti F., Perfetti V. Systematic analysis of human oncogenic viruses in colon cancer revealed EBV latency in lymphoid infiltrates. Infect Agent Cancer 2014; 9: 18, https://doi.org/10.1186/1750-9378-9-18.
43. Salyakina D., Tsinoremas N.F. Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data. Hum Genomics 2013; 7(1): 23, https://doi.org/10.1186/1479-7364-7-23.
44. Khoury J.D., Tannir N.M., Williams M.D., Chen Y., Yao H., Zhang J., Thompson E.J.; TCGA Network, Meric-Bernstam F., Medeiros L.J., Weinstein J.N., Su X. Landscape of DNA virus associations across human malignant cancers: analysis of 3,775 cases using RNA-Seq. J Virol 2013; 87(16): 8916–8926, https://doi.org/10.1128/jvi.00340-13.
45. Delaney D., Chetty R. Lymphoepithelioma-like carcinoma of the colon. Int J Clin Exp Pathol 2012; 5(1): 105–109.
46. Karpinski P., Myszka A., Ramsey D., Kielan W., Sasiadek M.M. Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype. Tumour Biol 2011; 32(4): 653–659, https://doi.org/10.1007/s13277-011-0165-6.
47. Chang H., Chuang W.Y., Shih L.Y., Tang T.C. Collision in the colon: concurrent adenocarcinoma and diffuse large B-cell lymphoma in the same tumour. Acta Clin Belg 2011; 66(4): 302–304.
48. Park J.M., Choi M.G., Kim S.W., Chung I.S., Yang C.W., Kim Y.S., Jung C.K., Lee K.Y., Kang J.H. Increased incidence of colorectal malignancies in renal transplant recipients: a case control study. Am J Transplant 2010; 10(9): 2043–2050, https://doi.org/10.1111/j.1600-6143.2010.03231.x.
49. Nishigami T., Kataoka T.R., Torii I., Sato A., Tamura K., Hirano H., Hida N., Ikeuchi H., Tsujimura T. Concomitant adenocarcinoma and colonic non-Hodgkin’s lymphoma in a patient with ulcerative colitis: a case report and molecular analysis. Pathol Res Pract 2010; 206(12): 846–850, https://doi.org/10.1016/j.prp.2010.07.007.
50. Militello V., Trevisan M., Squarzon L., Biasolo M.A., Rugge M., Militello C., Palù G., Barzon L. Investigation on the presence of polyomavirus, herpesvirus, and papillomavirus sequences in colorectal neoplasms and their association with cancer. Int J Cancer 2009; 124(10): 2501–2503, https://doi.org/10.1002/ijc.24224.
51. Song L.B., Zhang X., Zhang C.Q., Zhang Y., Pan Z.Z., Liao W.T., Li M.Z., Zeng M.S. Infection of Epstein–Barr virus in colorectal cancer in Chinese. Ai Zheng 2006; 25(11): 1356–1360.
52. Wong N.A.C.S., Herbst H., Herrmann K., Kirchner T., Krajewski A.S., Moorghen M., Niedobitek F., Rooney N., Shepherd N.A., Niedobitek G. Epstein–Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas. J Pathol 2003; 201(2): 312–318, https://doi.org/10.1002/path.1442.
53. Grinstein S., Preciado M.V., Gattuso P., Chabay P.A., Warren W.H., De Matteo E., Gould V.E. Demonstration of Epstein–Barr virus in carcinomas of various sites. Cancer Res 2002; 62(17): 4876–4878.
54. Kon S., Kasai K., Tsuzuki N., Nishibe M., Kitagawa T., Nishibe T., Sato N. Lymphoepithelioma-like carcinoma of rectum: possible relation with EBV. Pathol Res Pract 2001; 197(8): 577–582, https://doi.org/10.1078/0344-0338-00130.
55. Kijima Y., Hokita S., Takao S., Baba M., Natsugoe S., Yoshinaka H., Aridome K., Otsuji T., Itoh T., Tokunaga M., Eizuru Y., Aikou T. Epstein–Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms. J Med Virol 2001; 64(4): 513–518, https://doi.org/10.1002/jmv.1079.
56. Cho Y.J., Chang M.S., Park S.H., Kim H.S., Kim W.H. In situ hybridization of Epstein–Barr virus in tumor cells and tumor-infiltrating lymphocytes of the gastrointestinal tract. Hum Pathol 2001; 32(3): 297–301, https://doi.org/10.1053/hupa.2001.22766.
57. Samaha S., Tawfik O., Horvat R., Bhatia P. Lymphoepithelioma-like carcinoma of the colon: report of a case with histologic, immunohistochemical, and molecular studies for Epstein–Barr virus. Dis Colon Rectum 1998; 41(7): 925–928, https://doi.org/10.1007/bf02235379.
58. Vilor M., Tsutsumi Y. Localization of Epstein–Barr virus genome in lymphoid cells in poorly differentiated adenocarcinoma with lymphoid stroma of the colon. Pathol Int 1995; 45(9): 695–697, https://doi.org/10.1111/j.1440-1827.1995.tb03524.x.
59. Yuen S.T., Chung L.P., Leung S.Y., Luk I.S., Chan S.Y., Ho J. In situ detection of Epstein–Barr virus in gastric and colorectal adenocarcinomas. Am J Surg Pathol 1994; 18(11): 1158–1163, https://doi.org/10.1097/00000478-199411000-00010.
60. Boguszaková L., Hirsch I., Brichácek B., Faltýn J., Fric P., Dvoráková H., Vonka V. Absence of cytomegalovirus, Epstein–Barr virus, and papillomavirus DNA from adenoma and adenocarcinoma of the colon. Acta Virol 1988; 32(4): 303–308.
61. Nonoyama M., Kawai Y., Huang C.H., Pagano J.S., Hirshaut Y., Levine P.H. Epstein–Barr virus DNA in Hodgkin’s disease, American Burkitt’s lymphoma, and other human tumors. Cancer Res 1974; 34(5): 1228–1231.
62. Cajuso T., Hänninen U.A., Kondelin J., Gylfe A.E., Tanskanen T., Katainen R., Pitkänen E., Ristolainen H., Kaasinen E., Taipale M., Taipale J., Böhm J., Renkonen-Sinisalo L., Mecklin J.P., Järvinen H., Tuupanen S., Kilpivaara O., Vahteristo P. Exome sequencing reveals frequent inactivating mutations in ARID1A, ARID1B, ARID2 and ARID4A in microsatellite unstable colorectal cancer. Int J Cancer 2014; 135(3): 611–623, https://doi.org/10.1002/ijc.28705.
63. Ling C., Wang L., Wang Z., Xu L., Sun L., Yang H., Li W.D., Wang K. A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas. PLoS One 2015; 10(1): e0116753, https://doi.org/10.1371/journal.pone.0116753.
64. Kim Y.S., Jeong H., Choi J.W., Oh H.E., Lee J.H. Unique characteristics of ARID1A mutation and protein level in gastric and colorectal cancer: a meta-analysis. Saudi J Gastroenterol 2017; 23(5): 268–274, https://doi.org/10.4103/sjg.sjg_184_17.
65. Hay E.D. An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) 1995; 154(1): 8–20, https://doi.org/10.1159/000147748.
66. Al Moustafa A.E., Achkhar A., Yasmeen A. EGF-receptor signaling and epithelial-mesenchymal transition in human carcinomas. Front Biosci (Schol Ed) 2012; 4: 671–684, https://doi.org/10.2741/s292.
67. Tsai J.H., Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 2013; 27(20): 2192–2206, https://doi.org/10.1101/gad.225334.113.
68. Thiery J.P., Acloque H., Huang R.Y., Nieto M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139(5): 871–890, https://doi.org/10.1016/j.cell.2009.11.007.
69. Scanlon C.S., Van Tubergen E.A., Inglehart R.C., D’Silva N.J. Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res 2013; 92(2): 114–121, https://doi.org/10.1177/0022034512467352.
70. Tam W.L., Weinberg R.A. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med 2013; 19(11): 1438–1449, https://doi.org/10.1038/nm.3336.
71. Chen X., Bode A.M., Dong Z., Cao Y. The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer. FASEB J 2016; 30(9): 3001–3010, https://doi.org/10.1096/fj.201600388r.
72. Lin Z., Wan X., Jiang R., Deng L., Gao Y., Tang J., Yang Y., Zhao W., Yan X., Yao K., Sun B., Chen Y. Epstein–Barr virus-encoded latent membrane protein 2A promotes the epithelial-mesenchymal transition in nasopharyngeal carcinoma via metastatic tumor antigen 1 and mechanistic target of rapamycin signaling induction. J Virol 2014; 88(20): 11872–11885, https://doi.org/10.1128/jvi.01867-14.
73. Gaur N., Gandhi J., Robertson E.S., Verma S.C., Kaul R. Epstein–Barr virus latent antigens EBNA3C and EBNA1 modulate epithelial to mesenchymal transition of cancer cells associated with tumor metastasis. Tumour Biol 2015; 36(4): 3051–3060, https://doi.org/10.1007/s13277-014-2941-6.
74. Cai L.M., Lyu X.M., Luo W.R., Cui X.F., Ye Y.F., Yuan C.C., Peng Q.X., Wu D.H., Liu T.F., Wang E., Marincola F.M., Yao K.T., Fang W.Y., Cai H.B., Li X. EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN. Oncogene 2015; 34(17): 2156–2166, https://doi.org/10.1038/onc.2014.341.
75. He B., Li W., Wu Y., Wei F., Gong Z., Bo H., Wang Y., Li X., Xiang B., Guo C., Liao Q., Chen P., Zu X., Zhou M., Ma J., Li X., Li Y., Li G., Xiong W., Zeng Z. Epstein–Barr virus-encoded miR-BART6-3p inhibits cancer cell metastasis and invasion by targeting long non-coding RNA LOC553103. Cell Death Dis 2016; 7(9): e2353, https://doi.org/10.1038/cddis.2016.253.
76. Zuo L.L., Zhang J., Liu L.Z., Zhou Q., Du S.J., Xin S.Y., Ning Z.P., Yang J., Yu H.B., Yue W.X., Wang J., Zhu F.X., Li G.Y., Lu J.H. Cadherin 6 is activated by Epstein–Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma. Oncogenesis 2017; 6(12): 402, https://doi.org/10.1038/s41389-017-0005-7.
77. Mjelle R., Sjursen W., Thommesen L., Sætrom P., Hofsli E. Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location. BMC Cancer 2019; 19(1): 161, https://doi.org/10.1186/s12885-019-5330-0.
78. Rizzo A.G., Orlando A., Gallo E., Bisanti A., Sferrazza S., Montalbano L.M., Macaluso F.S., Cottone M. Is Epstein–Barr virus infection associated with the pathogenesis of microscopic colitis? J Clin Virol 2017; 97: 1–3, https://doi.org/10.1016/j.jcv.2017.10.009.
79. Nissen L.H.C., Nagtegaal I.D., de Jong D.J., Kievit W., Derikx L.A.A.P., Groenen P.J.T.A., van Krieken J.H.M., Hoentjen F. Epstein–Barr virus in inflammatory bowel disease: the spectrum of intestinal lymphoproliferative disorders. J Crohns Colitis 2015; 9(5): 398–403, https://doi.org/10.1093/ecco-jcc/jjv040.
80. Ryan J.L., Shen Y.J., Morgan D.R., Thorne L.B., Kenney S.C., Dominguez R.L., Gulley M.L. Epstein–Barr virus infection is common in inflamed gastrointestinal mucosa. Dig Dis Sci 2012; 57(7): 1887–1898, https://doi.org/10.1007/s10620-012-2116-5.
81. Spieker T., Herbst H. Distribution and phenotype of Epstein–Barr virus-infected cells in inflammatory bowel disease. Am J Pathol 2000; 157(1): 51–57, https://doi.org/10.1016/s0002-9440(10)64516-6.

Oleynikova N.A., Danilova N.V., Grimuta M.O., Malkov P.G. Epstein–Barr Virus in the Development of Colorectal Cancer (Review). Sovremennye tehnologii v medicine 2021; 13(4): 82, https://doi.org/10.17691/stm2021.13.4.09