Epstein-Barr virus (EBV) in Russia: infection of the population and analysis of the LMP1 gene variants in patients with EBV-associated pathologies and healthy individuals

Cover Page

Cite item

Full Text

Abstract

The Epstein-Barr virus, widespread herpesvirus among the population of the planet, is also the etiologic agent for a number of malignancies. One of the oncoproteins encoded by the virus, the latent membrane protein 1 (LMP1), through activation of the complex signaling pathways is involved in the processes of cell immortalization and transformation. The goal of this work was to study the level of the EBV infection in Russian population and LMP1 polymorphism in patients with benign and malignant EBV-associated diseases and healthy virus carriers. Studies have shown that by the age of 5-9 years the percentage of the infected persons and the level of antibody titers reaches almost the maximum values. With the age, virus specific antibody titers are decreased (with a high percentage of infected persons) and increased again in groups of older persons. The analysis of the nucleotide sequences of the gene LMP1 translated in amino acid (aa) sequences unexpectedly revealed the dominance a low divergent variant LMP1 B95.8A not only in healthy individuals but also in patients with all forms of EBV-associated diseases. Highly divergent variants Ch1 and Med +, containing a deletion of 10 aa, and characterized by elevated transforming activity more often were detected in the tumor tissue samples than in the blood samples/mouth washes of the same patients. Detection of highly transforming variant LMP1 Ch1 in blood samples of healthy individuals indicates that this analog of Chinese variant Cao may persist in any population and is not necessarily associated with the occurrence of the EBV-associated disorders.

About the authors

E. V. Goncharova

Federal State Budgetary Sientific Institution «N.N.Blokhin Cancer Research Center»

Author for correspondence.
Email: goncharova@dna-tech.ru

Elena Goncharova, candidate of biological Sciences

115478, Moscow

Russian Federation

N. B. Senyuta

Federal State Budgetary Sientific Institution «N.N.Blokhin Cancer Research Center»

Email: fake@neicon.ru
115478, Moscow Russian Federation

K. V. Smirnova

Federal State Budgetary Sientific Institution «N.N.Blokhin Cancer Research Center»

Email: fake@neicon.ru
115478, Moscow Russian Federation

L. N. Shcherbak

Federal State Budgetary Sientific Institution «N.N.Blokhin Cancer Research Center»

Email: fake@neicon.ru
115478, Moscow Russian Federation

V. E. Gurtsevich

Federal State Budgetary Sientific Institution «N.N.Blokhin Cancer Research Center»

Email: fake@neicon.ru
115478, Moscow Russian Federation

References

  1. Young L.S., Rickinson A.B. Epstein-Barr virus: 40 years on. Nat. Rev. Cancer. 2004; 4(10): 757–68.
  2. Young L.S., Murray P.G. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene. 2003; 22(33): 5108–21.
  3. Rickinson A. Epstein-Barr virus. Virus Res. 2002; 82(1-2): 109–13.
  4. Kaye K.M., Izumi K.M., Kieff E. Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc. Natl. Acad. Sci. U. S. A 1993; 90(19): 9150-54.
  5. Moorthy R.K., Thorley-Lawson D.A. All three domains of the EpsteinBarr virus-encoded latent membrane protein LMP-1 are required for transformation of rat-1 fibroblasts. J. Virol. 1993; 67(3): 1638–46.
  6. Dirmeier U., Neuhierl B., Kilger E., Reisbach G., Sandberg M.L., Hammerschmidt W. Latent membrane protein 1 is critical for efficient growth transformation of human B cells by epstein-barr virus. Cancer Res. 2003; 63(11): 2982–9.
  7. Eliopoulos A.G., Young L.S. LMP1 structure and signal transduction. Semin. Cancer Biol. 2001; 11(6): 435–44.
  8. Hu L.F., Zabarovsky E.R., Chen F., Cao S.L., Ernberg I., Klein G. et al. Isolation and sequencing of the Epstein-Barr virus BNLF-1 gene (LMP1) from a Chinese nasopharyngeal carcinoma. J. Gen. Virol. 1991; 72 (10): 2399–409.
  9. Hu L.F., Chen F., Zheng X., Ernberg I., Cao S.L., Christensson B. et al. Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1. Oncogene. 1993; 8(6): 1575–83.
  10. Смирнова K.В., Дидук С.В., Гурцевич В.Э. Функциональный анализ вариантов латентного мембранного белка 1 (LMP1) вируса Эпштейна-Барр у больных лимфопролиферативными заболеваниями. Биомедицинская химия. 2011; 57(1): 114–26.
  11. Dawson C.W., Port R.J., Young L.S. The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC). Semin. Cancer Biol. 2012; 22(2): 144–53.
  12. Horikawa T., Yoshizaki T., Kondo S., Furukawa M., Kaizaki Y., Pagano J.S. Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma. Br. J. Cancer. 2011; 104(7): 1160–67.
  13. Kung C.P., Meckes D.G., Jr., Raab-Traub N. Epstein-Barr virus LMP1 activates EGFR, STAT3, and ERK through effects on PKCdelta. J. Virol. 2011; 85(9): 4399–08.
  14. Fahraeus R., Rymo L., Rhim J.S., Klein G. Morphological transformation of human keratinocytes expressing the LMP gene of EpsteinBarr virus. Nature. 1990; 345(6274): 447–9.
  15. Chen M.L., Tsai C.N., Liang C.L., Shu C.H., Huang C.R., Sulitzeanu D. et al. Cloning and characterization of the latent membrane protein (LMP) of a specific Epstein-Barr virus variant derived from the nasopharyngeal carcinoma in the Taiwanese population. Oncogene. 1992; 7(11): 2131–40.
  16. Miller W.E., Cheshire J.L., Baldwin A.S.Jr., Raab-Traub N. The NPC derived C15 LMP1 protein confers enhanced activation of NF-kappa B and induction of the EGFR in epithelial cells. Oncogene. 1998; 16(14): 1869–77.
  17. Walling D.M., Shebib N., Weaver S.C., Nichols C.M., Flaitz C.M., Webster-Cyriaque J. The molecular epidemiology and evolution of EpsteinBarr virus: sequence variation and genetic recombination in the latent membrane protein-1 gene. J. Infect. Dis. 1999; 179(4): 763–74.
  18. Edwards R.H., Seillier-Moiseiwitsch F., Raab-Traub N. Signature amino acid changes in latent membrane protein 1 distinguish Epstein-Barr virus strains. Virology. 1999; 261(1): 79–95.
  19. Nitta T., Chiba A., Yamamoto N., Yamaoka S. Lack of cytotoxic property in a variant of Epstein-Barr virus latent membrane protein-1 isolated from nasopharyngeal carcinoma. Cell. Signal. 2004; 16(9): 1071–81.
  20. Sandvej K., Munch M., Hamilton-Dutoit S. Mutations in the EpsteinBarr virus latent membrane protein-1 (BNLF-1) gene in spontaneous lymphoblastoid cell lines: effect on in vitro transformation associated parameters and tumorigenicity in SCID and nude mice. Clin. Mol. Pathol. 1996; 49(5): 290–7.
  21. Zhou X.G., Sandvej K., Li P.J., Ji X.L., Yan Q.H., Zhang X.P. et al. Epstein–Barr virus gene polymorphisms in Chinese Hodgkin’s disease cases and healthy donors: identification of three distinct virus variants. J. Gen. Virol. 2001; 82(Pt 5): 1157–67.
  22. Mainou B.A., Raab-Traub N. LMP1 strain variants: biological and molecular properties. J. Virol. 2006; 80(13): 6458–68.
  23. Tang W., Pavlish O.A., Spiegelman V.S., Parkhitko A.A., Fuchs S.Y. Interaction of Epstein-Barr virus latent membrane protein 1 with SCFHOS/beta-TrCP E3 ubiquitin ligase regulates extent of NF-kappaB activation. J. Biol. Chem. 2003; 278(49): 48942–9.
  24. Hahn P., Novikova E., Scherback L., Janik C., Pavlish O., Arkhipov V. et al. The LMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion. Int. J. Cancer 2001; 91(6): 815-21.
  25. Gurtsevitch V., Ruiz R., Stepina V., Plachov I., Le Riverend E., Glazkova T. et al. Epstein-Barr viral serology in nasopharyngeal carcinoma patients in the USSR and Cuba, and its value for differential diagnosis of the disease. Int. J. Cancer. 1986; 37(3): 375–81.
  26. Cui Y., Wang Y., Liu X., Chao Y., Xing X., Zhao C. et al. Genotypic analysis of Epstein-Barr virus isolates associated with nasopharyngeal carcinoma in Northern China. Intervirology. 2011; 54(3): 131–8.
  27. Павлиш O.A., Дидук С.В., Смирнова K.В., Щербак Л.Н., Гончарова E.В., Шалгинских Н.A. и др. Мутации гена LMP1 вируса Эпштейна–Барр у российских больных лимфоидной патологией и здоровых лиц. Вопросы вирусологии. 2008; 53(1): 10–6.
  28. Sitki-Green D., Covington M., Raab-Traub N. Compartmentalization and transmission of multiple epstein-barr virus strains in asymptomatic carriers. J. Virol. 2003; 77(3): 1840–7.
  29. Nitta T., Chiba A., Yamamoto N., Yamaoka S. Lack of cytotoxic property in a variant of Epstein-Barr virus latent membrane protein-1 isolated from nasopharyngeal carcinoma. Cell Signal. 2004; 16(9): 1071–81.
  30. Faumont N., Chanut A., Benard A., Cogne N., Delsol G., Feuillard J. et al. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin’s lymphoma’s Reed-Sternberg cells and normal Blymphocytes. Haematologica. 2009; 94(3): 355–63.
  31. Nagamine M., Takahara M., Kishibe K., Nagato T., Ishii H., Bandoh N. et al. Sequence variations of Epstein-Barr virus LMP1 gene in nasal NK/T-cell lymphoma. Virus Genes. 2007; 34(1): 47–54.
  32. Дидук С.В., Смирнова K.В., Павлиш O.A., Гурцевич В.Э. Роль функционально значимых мутаций гена LMP1 вируса Эпштейна–Барр в активации клеточных сигнальных путей. Биохимия. 2008; 73(10): 1414–21.
  33. Sandvej K., Gratama J.W., Munch M., Zhou X.G., Bolhuis R.L., Andresen B.S. et al. Sequence analysis of the Epstein-Barr virus (EBV) latent membrane protein-1 gene and promoter region: identification of four variants among wild-type EBV isolates. Blood. 1997; 90(1): 323–30.
  34. Gires O., Kohlhuber F., Kilger E., Baumann M., Kieser A., Kaiser C. et al. Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and and activates STAT proteins. EMBO J. 1999; 18(11): 3064–73.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2015 Goncharova E.V., Senyuta N.B., Smirnova K.V., Shcherbak L.N., Gurtsevich V.E.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС77-77676 от 29.01.2020.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies