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Epstein-Barr virus

This section contains information on Epstein-Barr virus including Post-transplant lymphoma, Burkitt's lymphoma, Hodgkin's lymphoma and nasopharyngeal carcinoma.

Epstein-Barr virus is a herpesvirus that is widespread in all human populations. Infection usually occurs in childhood but if delayed until adolescence can result in infectious mononucleosis (glandular fever). EBV is distantly related to other herpesviruses like herpes simplex (the cause of cold sores) or varicella-zoster e (the cause of chicken pox).Like them, EBV can replicate fully in epithelial cells, in this case in pharyngeal cells lining the inner mucosal surfaces of the mouth and nose.

Unlike other herpesviruses, Epstein-Barr virus has a unique set of growth activating genes which it uses to establish a latent growth-transforming infection of its main target cell, the B lymphocyte. The growth of latently-infected B cells is normally controlled by the host immune response, particularly the T cell response, and so the great majority of people are able to carry this potentially dangerous virus all their life without any ill effect. In certain circumstances,however, long-term virus carriage can result in the appearance a number of EBV-positive tumours1-3 (Figure 4.1).

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Post-transplant lymphoma

Patients receiving T cell-suppressive drugs to prevent rejection of a transplanted organ have reduced immune control over various persistent virus infections, including EBV. Strongly immunosuppressed patients are at high risk of developing 'post-transplant lymphoma' (PTL), a tumour caused by EBV-transformed B cells growing out in the absence of T cell control4. A similar tumour is seen in late-stage AIDS patients whose T cell control has been destroyed by HIV infection5.

Burkitt lymphoma

EBV is also strongly linked to a second B cell tumour, endemic Burkitt lymphoma (BL), the commonest cancer of childhood in many parts of equatorial Africa and in New Guinea (Figure 4.2).

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Every tumour is EBV genome-positive and continues to express at least one virus latent protein. In addition, every tumour has acquired a chromosomal translocation leading to uncontrolled expression of the cellular oncogene, c-myc. EBV infection and the c-myc translocation appear to be independent changes that together drive the B cell to full malignancy. Chronic malarial infection is another key co-factor in tumour development and this explains the unusual geographic distribution of the disease. The malarial parasite is thought to act as a chronic immune stimulus to B cells, increasing the number of cells in active growth and therefore at risk of accidental c-myc translocation.1 BL is a rare childhood tumour in the Western world.Over the last 25 years, however, BL has appeared unexpectedly in HIV infected adults as an early symptom of AIDS, with HIV seeming to mimic some of the chronic immune stimulation seen from malaria in Africa. In contrast to endemic BL, only a minority of childhood and AIDS-associated BL are EBV positive1-5.

Hodgkin's lymphoma

Hodgkin's lymphoma (HL) is a third tumour of B cell origin that is linked to EBV. The disease occurs in all human populations at a roughly similar frequency. Some 40% of HL cases in Western countries are EBV genome-positive, and the association with EBV is even higher in many other parts of the world. Cellular genetic changes, as yet poorly understood, are crucial to HL development. In those tumours where EBV is present, the continued expression of a number of key viral latent proteins strongly suggests that the virus is contributing actively to tumour growth6.

Nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a cancer of the epithelial cells lining the nasal cavity. It is seen worldwide but is most common throughout South East Asia, especially in southern China (Figure 4.2). All cases of NPC worldwide are EBV-associated and express viral latent proteins in every cell, strongly suggesting that the virus is key to tumour development. The difference in NPC incidence in different human populations cannot be explained by the prevalence of EBV infection, since most people worldwide carry the virus. Instead it is thought to reflect the essential role of two other co-factors in NPC development, firstly some genetic susceptibility among southern Chinese, South East Asian and Inuit people and secondly the influence of chemical carcinogens in the local diet.2, 7

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References for Epstein Barr virus and cancer

1. Rickinson, A.B. and E. Kieff, Epstein-Barr virus in Fields Virology. ed., ed. D. Knipe and P. Howley. Vol. 2001, Philadelphia: Lippincott Williams and Wilkins.
2. Young, L.S. and A.B. Rickinson, Epstein-Barr virus: 40 years on. Nat Rev Cancer, 2004. 4(10): p. 757-68.PubMed
3. IARC, IARC Monograph on the evaluation of carcinogenic risks to Humans Volume 67. Epstein-Barr virus and Kaposi sarcoma herpesvirus/Human herpesvirus 8. 1997. p.PubMed
4. Gottschalk, S., C. Rooney, and H. Heslop, Post-transplant lymphoproliferative disorders. Ann Rev Med, 2005. 56: p. 29-44.PubMed
5. Carbone, A., Emerging pathways in the development of AIDS related lymphomas. Lancet Oncol, 2003. 4(1): p. 22-29.PubMed
6. Kuppers, R., B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol, 2003. 3(10): p. 801-812.PubMed
7. Raab-Traub, N., Epstein-Barr virus in the pathogenesis of NPC. Semin Cancer Biol, 2002. 12(6): p. 431-444.PubMed

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