REVIEW PAPER
Epstein-Barr Virus – pathogenesis, latency and cancers
 
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Medical University of Lublin, Department of Virology
 
 
Corresponding author
Ewa Kliszczewska   

Medical University of Lublin, Department of Virology, Al. Racławickie 1, 20-059 Lublin, Poland
 
 
J Pre Clin Clin Res. 2017;11(2):142-146
 
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ABSTRACT
Abstract:
The Epstein-Barr virus (EBV) was discovered in 1964 by Michael Anthony Epstein and Yvonne Barr, who discovered a herpesvirus-like infectious agent in a biopsy specimen from a patient with Burkitt's lymphoma. This virus belongs to the Herpesviridae family (subfamily Gammaherpesvirinae, genus Lymphocryptovirus). EBV is a ubiquitous herpesvirus that is causally associated with various malignant tumours. According to the current nomenclature, it was named human herpesvirus type 4 (human herpesvirus 4 - HHV-4). Primary infection usually occurs in childhood. In developing countries, the infection rate among young children is higher than in developed countries. It was the first human tumour virus and it is currently categorized as a group-1 carcinogen due to its association with various cancers. It is estimated that over 90% of the adult population has been infected with this pathogen, but only a minority will develop the disease. EBV establishes latent infection characterized by the expression of a limited number of viral genes called latent genes. Moreover, during its life cycle, EBV periodically reactivates and can be transmitted to other susceptible hosts. The oral cavity is the main site of EBV occurrence and the most common source of infection. This study discusses EBV frequency and its association with the occurrence of malignant tumours and the pathways of tumour progression.

 
REFERENCES (50)
1.
Abdulamir AS, Hafidh RR, Abu Bakar F, Abbas K. Novel Epstein-Barr virus immunoglobulin G-based approach for the specific detection of nasopharyngeal carcinoma. Am. J Otolaryngol. 2010; 31(6): 410-417.
 
2.
Andersson J. Epstein-Barr virus and Hodgkin's lymphoma. Herpes. 2006; 13:12-16.
 
3.
Glickman JN, Howe JG, Steitz JA. Structural analyses of EBER1 and EBER2 ribonucleoprotein particles present in Epstein-Barr virus-infected cells. J Virol. 1988; 62(3): 902–911.
 
4.
Beaulieu BL, Sullivan JL. Epstein- Barr Virus. Clinical Virology. 2005; 479- 493.
 
5.
Epstein MA, Achong B, Barr YM. Virus particles in cultured lymphoblast from Burkitt’s lymphoma. Lancet. 1964; 1: 702–703.
 
6.
Epstein MA, Achong BG, Barr Y M. Morphological and biological studies on a virus in cultured lymphoblasts from Burkitt lymphoma. J Exp Med. 1965; 121: 761–770.
 
7.
Macsween KF, Higgins CD, McAulay KA, Williams H, Harrison N, Swerdlow AJ, et al. Infectious mononucleosis in university students in the United Kingdom: evaluation of the clinical features and consequences of the disease. Clin Infect Dis. 2010; 50(5): 699–706.
 
8.
Crawford DH. Biology and disease associations of Epstein-Barr virus. Philos Trans R Soc Lond B Biol Sci. 2001; 356(1408): 461-473.
 
9.
Young LS, Rickinson AB. Epstein–Barr virus: 40 years on. Nat Rev Cancer. 2004; 4(10): 757-768.
 
10.
Stefanko E, Wróbel T. Etiopatogeneza infekcyjna chłoniaków. Hematol. 2010; 1(4): 288-295.
 
11.
Bocian J, Januszkiewicz-Lewandowska D. Epstein-Barr virus infection – life cycle, methods of diagnosis, associates diseases. Postepy Hig Med Dosw. 2011; 65: 286-298.
 
12.
Żuk-Wasek A. Characterization of Epstein-Barr virus proteins – their participation in latency and relation to oncogenesis. Post. Mikrobiol. 2012; 51(3): 191–201.
 
13.
Tsao SW, Tsang CM, To KF, Lo KW. The role of Epstein-Barr virus in epithelial malignancies. J Pathol. 2015; 235(2): 323-333.
 
14.
Dobrzańska J, Sawczuk-Chabin J, Warzocha K. The role of viruses in etiopathogenesis of non-Hodgkin lymphomas. Onkol Clin Pract. 2006; 2(2): 65-72.
 
15.
Thompson MP, Kurzrock R. Epstein-Barr virus and cancer. Clin Cancer Res. 2004; 10: 803–821.
 
16.
Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene. 2003; 22(33): 5108-5121.
 
17.
Tiwawech D, Srivatankul P, Karalak A, Ishida T. Association between EBNA2 and LMP1 subtypes of Epstein-Barr virus and nasopharyngeal carcinoma in Thais. J Clin Virol. 2008; 42(1):1-6.
 
18.
Warzocha K, Juszczyński P, Biliński P, Czyż J. Postępy w biologii i leczeniu chłoniaka Hodgkina. Onkol Prakt Klin. 2005; 1:83-95.
 
19.
Polz D, Podsiadło Ł, Stec A, Polz-Dacewicz M. Prevalence of EBV genotypes in Polish, Taiwanese and Arabic healthy students and association between genotypes and 30-bp deletion in the LMP-1 gene phylogenetic analysis. Pol J Microbiol. 2014; 63(1):105-109.
 
20.
IARC monographs on the evaluation of carcinogenic risks to humans A review of human carcinogens. Biological agents, Lyon, France. World Health Organization. 2012; 255.
 
21.
Rickinson AB. Co-infections, inflammation and oncogenesis: future directions for EBV research. Semin Cancer Biol. 2014; 26: 99-115.
 
22.
Siennicka J, Trzcińska A. Laboratoryjna diagnostyka zakażeń EBV. Med Dośw Mikrobiol. 2007; 59: 259-266.
 
23.
Acharya S, Ekalaksananan T, Vatanasapt P, Loyha K, Phusingha P, Promthet S, et al. Association of Epstein-Barr virus infection with oral squamous cell carcinoma in a case-control study. J Oral Pathol Med. 2014; 43: 507-13.
 
24.
Baltzell K, Buehring G, Krishnamurthy S. Epstein-Barr virus is seldom found in mammary epithelium of breast cancer tissue using in situ molecular methods. Breast Cancer Res Treat. 2012; 132(1): 267-274.
 
25.
Chen CJ, Hsu WL, Yang HI, Lee MH, Chen HC, Chien YC, et al. Epidemiology of virus infection and human cancer. Recent Results Cancer Res. 2014; 193:11-32.
 
26.
Chen XZ, Che H, Castro FH, Hu J, Brenner H. Epstein-Barr virus infection and gastric cancer: a systematic review. Medicine. 2015; 94(20): e792.
 
27.
Jalouli J, Jalouli MM, Sapkota D, Ibrahim SO, Larson PA, Sand L. Human papilloma virus, herpes simplex and Epstein-Barr virus in oral squamous cell carcinoma from eight different countries. Anticancer Res. 2012; 32: 571-80.
 
28.
Jalouli J, Ibrahim S, Sapkota D, Jalouli MM, Vasstrand EN, Hirsch JM, et al. Prevalence of human papilloma virus, herpes simplex virus and Epstein-Barr virus DNA in oral biopsies from Sudanese patients with regard to toombak use. J Oral Pathology Med. 2011; 19: 599-604.
 
29.
Pattle SB, Farrell PJ. The role of Epstein-Barr virus in cancer. Expert Opin Biol Ther. 2006; 6(11): 1193-1205.
 
30.
Alibek K, Kakpenova A, Baiken Y. Role of infectious agents in the carcinogenesis of brain and head and neck cancers. Infect Agent Cancer. 2013; 8(1): 7.
 
31.
Jha HC, Banerjee S, Robertson ES. The Role of Gammaherpesviruses in Cancer Pathogenesis. Pathogens; 2016; 5(18): 1-43.
 
32.
Goldenberg D1, Benoit NE, Begum S, Westra WH, Cohen Y, Koch WM, et al. Epstein-Barr Virus in Head and Neck Cancer Assessed by Quantitative Polymerase Chain Reaction. The Laryngoscope. 2004; 114(6): 1027–1031.
 
33.
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513: 202-209.
 
34.
Polz-Gruszka D, Stec A, Dworzański J, Polz-Dacewicz M. EBV, HSV, CMV and HPV in laryngeal and oropharyngeal carcinoma in Polish patients. Anticancer Res. 2015; 35(3): 1657-1662.
 
35.
Sand L, Waastrom M, Hirsch JM. Smokeles tobacco, viruses and oral cancer. Oral Health Dent Manag. 2014; 13: 372-8.
 
36.
Burke AP, Yen TS, Shekitka KM, Sobin LH. Lymphoepithelial carcinoma of the stomach with the Epstein-Barr virus demonstrated by polymerase chain re action. Mod Pathol. 1990; 3(3): 377-380.
 
37.
Zur Hausen H. Biochemical approaches to detection of Epstein-Barr virus in human tumors. Cancer Res. 1976; 36(2 pt 2): 678-680.
 
38.
Zur Hausen A, Van Rees BP, Van Beek J, Craanen ME, Bloemena E, Offerhaus GJA, et al. Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis. J Clin Pathol. 2004; 57(5): 487–491.
 
39.
Shinozaki-Ushiku A, Kunita A, Fukyama M: Update on Epstein-Barr virus and gastric cancer. Int J Oncolo. 2015; 46(4): 1421-1434.
 
40.
Murphy G, Pfeifer R, Camargo MC, Rabkin CS. Meta-analysis show that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology. 2009; 137(3): 824-833.
 
41.
Camargo MC, Kim WH, Chiaravalli AM, Kim KM, Corvalan AH, Matsuo K,et al. Improved survival of gastric cancer with tumor Epstein-Barr virus positivity: an international pooled analysis. Gut. 2014; 63(2): 236-243.
 
42.
Camargo MC, Murphy G, Koriyama C, Pfeiffer RM, Kim WH, Herrera-Goepfert R, et al. Determinations of Epstein-Barr virus-positive gastric cancer: an international pooled analysis. Br J Cancer. 2011; 105(1): 38-43.
 
43.
Cohen JI, Fauci AS, Varmus H, Nabel GJ. Epstein –Barr virus: an important vaccine target for cancer prevention. Sci Transl Med. 2011; 3(107): 107fs7.
 
44.
Bae JM, Kim EH. Epstein-Barr virus and Gastric Cancer risk: A Meta-analysis with meta-regression of case-control studies. J Med Public Health. 2016, 49(2): 97-107.
 
45.
Liu S, Zhao Z, Han L, Liu S, Luo B. Epstein-Barr Virus Infection in Gastric Remnant Carcinoma and Recurrent Gastric Carcinoma in Qingdao of Northern China. PloS One. 2016; 11(2): e0148342.
 
46.
Cho J, Kang M, Kim KM. Epstein - Barr virus associated gastric carcinoma and specific features of the accompanying immune response. J Gastric Cancer. 2016; 16(1): 1-7.
 
47.
Kang MS, Kieff E. Epstein–Barr virus latent genes. Exp Mol Med. 2015; 47(1): e131.
 
48.
Shinkura R, Yamamoto N, Koriyama C, Shinmura Y, Eizuru Y, Tokunaga M. Epstein-Barr virus specific antibodies in EBV-positive and – negative gastric carcinoma cases in Japan. J Med Virol. 2000; 60(4): 411-416.
 
49.
Kayamba V, Monze M, Asombang AW, Zyambo K, Kelly P. Serological response to Epstein-Barr virus Elary antygen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a case-control study. Pan Afr Med J. 2016; 23: 45.
 
50.
Schetter A, You W, Lennette E, Goil M, Rabkin Ch. Association of Epstein-Barr virus antibody levels with precancerous gastric lessions in high-risk cohort. Cancer Sci. 2008; 99(2): 350-4.
 
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