Scientific Online Resource System

Scripta Scientifica Medica

Epstein-Barr virus - molecular basis for malignant transformation

Tsvetelina Kostadinova Popova, Tatina Todorova Todorova, Gabriela Staneva Tsankova, Lilia Ivanova Ivanova, Todor Rosenov Raykov, Neli Mitkova Ermenlieva, Emilia Petrova Georgieva

Abstract

Epstein-Barr (EBV) is a widespread virus which can be detected in more than 90% of world population. Primary EBV infection during adolescence and adultness results in infectious mononucleosis, while in children it is usually asymptomatic. EBV is responsible for different malignant forms of B-cell or epithelial cancers, such as Hodgkin's and non-Hodgkin`s lymphoma, Burkitt's lymphoma, post-transplant lymphoproliferative disorders, nasopharyngeal carcinoma, hairy leukoplakia and HIV-associated lymphomas. Evidence exists that infection with EBV is also linked with a higher risk of hepatocellular and gastric cancers, as well as autoimmune diseases.

EВV shows two alternative life cycles - latent and lytic. After the primary infection, the virus remains in B lymphocytes in latency, while the lytic infection takes place predominantly in the epithelial cells and can last for months with constant virus release in saliva and nasopharyngeal secretion. Unlike other herpes viruses, development of oncological diseases is linked with the latent cycle, as a result of immune response‘s failure to control latently infected cells.

With the present work we try to concisely review the current knowledge about mechanisms of EBV pathogenesis in humans and to summarize recent findings in the field.


Keywords

Epstein-Barr virus; ЕВV pathogenicity; EBV latency; malignant transformation

Full Text


References

References:

Dolyniuk M, Pritchett R, Kieff E. Proteins of Epstein-Barr virus. I. Analysis of the polypeptides of purified enveloped Epstein-Barr virus. J Virol. 1976 Mar;17(3):935-49.

Dolyniuk M, Wolff E, Kieff E. Proteins of Epstein-Barr Virus. II. Electrophoretic analysis of the polypeptides of the nucleocapsid and the glucosamine- and polysaccharide-containing components of enveloped virus. J Virol. 1976 Apr;18(1):289-97.

Kieff E, Rickinson AB. Epstein -Barr virus and its replication. In: Fields Virology. 2007. p. Fields Virology.

Tarbouriech N, Buisson M, Géoui T, Daenke S, Cusack S, Burmeister WP. Structural genomics of the Epstein-Barr virus. Acta Crystallogr D Biol Crystallogr. 2006 Oct;62(Pt 10):1276-85.

Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. Jan;310(5974):207-11.

Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000 Aug 17;343(7):481-92.

Epstein MA. Recent studies with EB virus. Yale J Biol Med. 1975 Nov;48(5):431-7.

Li QX, Young LS, Niedobitek G, Dawson CW, Birkenbach M, Wang F, et al. Epstein-Barr virus infection and replication in a human epithelial cell system. Nature. 1992 Mar 26;356(6367):347-50.

Molesworth SJ, Lake CM, Borza CM, Turk SM, Hutt-Fletcher LM. Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells. J Virol. 2000 Jul;74(14):6324-32.

Tugizov SM, Berline JW, Palefsky JM. Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells. Nat Med. 2003 Feb 18;9(3):307-14.

Xiao J, Palefsky JM, Herrera R, Tugizov SM. Characterization of the Epstein-Barr virus glycoprotein BMRF-2. Virology. 2007 Mar 15;359(2):382-96.

Gan YJ, Chodosh J, Morgan A, Sixbey JW. Epithelial cell polarization is a determinant in the infectious outcome of immunoglobulin A-mediated entry by Epstein-Barr virus. J Virol. 1997 Jan;71(1):519-26.

Sixbey JW, Yao QY. Immunoglobulin A-induced shift of Epstein-Barr virus tissue tropism. Science. 1992 Mar 20;255(5051):1578-80.

Shannon-Lowe CD, Neuhierl B, Baldwin G, Rickinson AB, Delecluse H-J. Resting B cells as a transfer vehicle for Epstein-Barr virus infection of epithelial cells. Proc Natl Acad Sci U S A. 2006 May 2;103(18):7065-70.

Näher H, Petzoldt D. [Epstein-Barr virus infection--a lympho- and epitheliotropic infection]. Hautarzt. 1992 Mar;43(3):114-9.

Niedobitek G, Young LS. Epstein-Barr virus persistence and virus-associated tumours. Lancet (London, England). 1994 Feb 5;343(8893):333-5.

Babcock GJ, Decker LL, Volk M, Thorley-Lawson DA. EBV persistence in memory B cells in vivo. Immunity. 1998 Sep;9(3):395-404.

Thorley-Lawson DA, Gross A. Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med. 2004 Mar 25;350(13):1328-37.

Heslop HE, Ng CY, Li C, Smith CA, Loftin SK, Krance RA, et al. Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med. 1996 May;2(5):551-5.

Qu L, Green M, Webber S, Reyes J, Ellis D, Rowe D. Epstein Barr Virus Gene Expression in the Peripheral Blood of Transplant Recipients with Persistent Circulating Virus Loads. J Infect Dis. 2000 Oct 1;182(4):1013-21.

Babcock GJ, Decker LL, Freeman RB, Thorley-Lawson DA. Epstein-barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients. J Exp Med. 1999 Aug 16;190(4):567-76.

Rowe M, Lear AL, Croom-Carter D, Davies AH, Rickinson AB. Three pathways of Epstein-Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol. 1992 Jan;66(1):122-31.

Tailleux L, Neyrolles O, Honore-Bouakline S, Perret E, Sanchez F, Abastado J-P, et al. Constrained Intracellular Survival of Mycobacterium tuberculosis in Human Dendritic Cells. J Immunol. American Association of Immunologists; 2003 Feb 15;170(4):1939-48.

Thorley-Lawson DA. Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol. 2001 Oct;1(1):75-82.

Tovey MG, Lenoir G, Begon-Lours J. Activation of latent Epstein-Barr virus by antibody to human IgM. Nature. 1978 Nov 16;276(5685):270-2.

Adler B, Schaadt E, Kempkes B, Zimber-Strobl U, Baier B, Bornkamm GW. Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):437-42.

Nathanson N. Viral Pathogenesis and Immunity. Academic Press; 2007. 280 p.

Knowles DM. Immunodeficiency-associated lymphoproliferative disorders. Mod Pathol. 1999 Feb;12(2):200-17.

Loren AW, Porter DL, Stadtmauer EA, Tsai DE. Post-transplant lymphoproliferative disorder: a review. Bone Marrow Transplant. 2003 Feb;31(3):145-55.

Raab-Traub N. Epstein-Barr virus in the pathogenesis of NPC. Semin Cancer Biol. 2002 Dec;12(6):431-41.

Hsu JL, Glaser SL. Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications. Crit Rev Oncol Hematol. 2000 Apr;34(1):27-53.

Yu MC, Yuan J-M. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):421-9.

Rowe M, Khanna R, Jacob CA, Argaet V, Kelly A, Powis S, et al. Restoration of endogenous antigen processing in Burkitt`s lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression. Eur J Immunol. 1995 May;25(5):1374-84.

Kulwichit W, Edwards RH, Davenport EM, Baskar JF, Godfrey V, Raab-Traub N. Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11963-8.

Laherty CD, Hu HM, Opipari AW, Wang F, Dixit VM. The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B. J Biol Chem. 1992 Dec 5;267(34):24157-60.

Gires O, Zimber-Strobl U, Gonnella R, Ueffing M, Marschall G, Zeidler R, et al. Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule. EMBO J. 1997 Oct 15;16(20):6131-40.

Kilger E, Kieser A, Baumann M, Hammerschmidt W. Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J. 1998 Mar 16;17(6):1700-9.

Huen DS, Henderson SA, Croom-Carter D, Rowe M. The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene. 1995 Feb 2;10(3):549-60.

Floettmann JE, Eliopoulos AG, Jones M, Young LS, Rowe M. Epstein-Barr virus latent membrane protein-1 (LMP1) signalling is distinct from CD40 and involves physical cooperation of its two C-terminus functional regions. Oncogene. 1998 Nov 5;17(18):2383-92.

Eliopoulos AG, Gallagher NJ, Blake SM, Dawson CW, Young LS. Activation of the p38 mitogen-activated protein kinase pathway by Epstein-Barr virus-encoded latent membrane protein 1 coregulates interleukin-6 and interleukin-8 production. J Biol Chem. 1999 Jun 4;274(23):16085-96.

Goldsmith DB, West TM, Morton R. HLA associations with nasopharyngeal carcinoma in Southern Chinese: a meta-analysis. Clin Otolaryngol Allied Sci. 2002 Feb;27(1):61-7.

Xiong W, Zeng ZY, Xia JH, Xia K, Shen SR, Li XL, et al. A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma. Cancer Res. 2004 Mar 15;64(6):1972-4.

Feng B-J, Huang W, Shugart YY, Lee MK, Zhang F, Xia J-C, et al. Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4. Nat Genet. 2002 Aug;31(4):395-9.




DOI: http://dx.doi.org/10.14748/ssm.v1i1.1442

Refbacks

About The Authors

Tsvetelina Kostadinova Popova
Medical College, Medical University of Varna
Bulgaria

Tatina Todorova Todorova
Department of Preclinical and Clinical Sciences, Medical University of Varna
Bulgaria

Gabriela Staneva Tsankova
Department of Preclinical and Clinical Sciences, Medical University of Varna

Lilia Ivanova Ivanova
Department of Microbiology and Virology, Medical University of Varna
Bulgaria

Todor Rosenov Raykov
Association of patients with rheumatoid arthritis

Neli Mitkova Ermenlieva
Medical College, Medical University of Varna
Bulgaria

Emilia Petrova Georgieva
Medical College, Medical University of Varna

Font Size


|