Epstein–Barr virus LMP1 oncogene polymorphism in tatar and slavic populations in Russian Federation impacting on some malignant tumours

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Abstract

Objective: To compare genetic structure of the main Epstein–Barr virus (EBV) oncogene, latent membrane protein 1 (LMP1), in EBV strains circulating in two genetically distinct ethnic populations in Russian Federation, Tatars and Slavs, as well as assess an impact of diverse LMP1 variants on incidence and mortality rate for some malignant tumors partially associated with EBV infection. Materials and methods. Oral washing samples were collected from 60 ethnic Kazan Tatars and 65 ethnic Moscow Slavics. Carboxy-terminal nucleotide sequences (41 and 40 sequences, respectively) derived from hypervariable LMP1 gene region were amplified from EBV DNA samples. Next, final nucleotide sequences were translated into amino acid sequences and analyzed according to classification by Edwards et al. Results. Analysis of 41 and 40 LMP1 samples obtained from ethnic Kasan Tatars and ethnic Moscow Slavics, respectively, revealed significant difference in relevant amino acid structures. In particular, all LMP1 samples derived from Moscow Slavics were found to belong to the four protein variants: B95.8/A, Med–, China1 and NC. Among them, low-transforming variant B95.8/A was dominant (82.5%). In contrast, solely 21 out of 41 LMP1 samples derived from ethnic Tatars were classified as B95.8/A, Med– and China1 variants. Importantly, the percentage of low-transforming B95.8/A variant among ethnic Tatar samples was significantly lower compared to that one found in Moscow Slavics (29.3% vs. 82.5%). On the other hand, seven (17.1%) out of 20 other samples formed a unique protein mono group characterized by LMP1 amino acid sequence differed from that one available in the GenBank database. Such group of variants was designated as LMP1-TatK. The remaining 13 samples (31.7%) did not match either protein variants, thereby forming the “beyond classification” (LMP1-TatBC) group. Conclusion. The data obtained suggest that various LMP1 variants exist in EBV strains persisting in ethnic Tatrs and ethnic Slavics examined in Russian Federation. It was also found that EBV strains isolated from ethnic Tatars contained a unique LMP1 gene variant encoding protein LMP1-TatK lacked in EBV strains derived from ethnic Moscow Slavics. Taking into account the genealogy of Tatars, it cannot be ruled out that EBV strain bearing LMP1-TatK variant represented ethnically specific EBV strain that might circulate many centuries ago among their historical human predecessors called Mongol-Tatar tribes. In addition, it was shown that the LMP1 variants in EBV strains isolated from ethnic Kazan Tatars and ethnic Moscow Slavics did not affect the incidence and mortality of different forms of cancer consisting of EBV-associated cases.

About the authors

V. E. Gurtsevitch

N.N. Blokhin National Medical Research Center of Oncology

Author for correspondence.
Email: gurtsevitch-vlad-88@yandex.ru
ORCID iD: 0000-0003-1840-4364

Vladimir E. Gurtsevitch – PhD, MD (Medicine), Professor, Laboratory of Viral Carcinogenesis

115478, Moscow, Kashirskoye highway, 24
Phone: +7 910 444-83-52 (mobile) 

Russian Federation

K. V. Smirnova

N.N. Blokhin National Medical Research Center of Oncology; Pirogov National Research Medical University

Email: skv.lab@yandex.ru
ORCID iD: 0000-0001-6209-977X

PhD (Biology), Head of the Laboratory of Viral Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology; Associate Professor, Department of Biochemistry and Molecular Biology, Pirogov National Research Medical University

Moscow

Russian Federation

I. V. Botezatu

N.N. Blokhin National Medical Research Center of Oncology

Email: botezatu@crc.umos.ru
ORCID iD: 0000-0002-0297-4963

PhD (Biology), Researcher, Tumor Biochemistry Group

Moscow

Russian Federation

T. E. Dushenkina

N.N. Blokhin National Medical Research Center of Oncology

Email: tatyana-duschenkina@yandex.ru

Investigator (Biologist), Laboratory of Viral Carcinogenesis

Moscow

Russian Federation

A. K. Lubenskaya

N.N. Blokhin National Medical Research Center of Oncology

Email: lubenskaya.96@mail.ru

Investigator (Biologist), Laboratory of Viral Carcinogenesis

Moscow

Russian Federation

E. Dubar

N.N. Blokhin National Medical Research Center of Oncology

Email: emeldubar@rambler.ru

Investigator (Biologist), Laboratory of Viral Carcinogenesis

Moscow

Russian Federation

N. B. Senyuta

N.N. Blokhin National Medical Research Center of Oncology

Email: nat.senyuta@yandex.ru
ORCID iD: 0000-0001-8915-8274

PhD (Medicine), Leading Researcher, Laboratory of Viral Carcinogenesis

Moscow

Russian Federation

A. V. Lichtenstein

N.N. Blokhin National Medical Research Center of Oncology

Email: alicth@mail.ru
ORCID iD: 0000-0002-0190-5069

PhD, MD (Biology), Leading Researcher, Tumor Biochemistry Group

Moscow

Russian Federation

S. V. Petrov

Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan

Email: semyonp@mail.ru

PhD, MD (Medicine), Professor, Head of the Laboratory of Immunohistochemical Diagnosis of Tumors

Kazan

Russian Federation

References

  1. Кривошеев Ю.В. Русь и монголы: исследование по истории Северо-Восточной Руси XII—XV вв. СПб.: Академия исследования культуры, 2015. 452 с.
  2. Состояние онкологической помощи населению России в 2017 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. Москва: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018. 236 c.
  3. Хрусталев Д.Г. Русь и монгольское нашествие (20–50 гг. XIII в.). СПб.: Евразия, 2015. 416 с.
  4. Alexander F.E., Jarrett R.F., Lawrence D., Armstrong A.A., Freeland J., Gokhale D.A., Kane E., Taylor G.M., Wright D.H., Cartwright R.A. Risk factors for Hodgkin’s disease by Epstein–Barr virus (EBV) status: prior infection by EBV and other agents. Br. J. Cancer, 2000, vol. 82, pp. 1117–1121. doi: 10.1054/bjoc.1999.1049
  5. Andreone P., Gramenzi A., Lorenzini S., Biselli M., Cursaro C., Pileri S., Bernardi M. Posttransplantation lymphoproliferative disorders. Arch. Intern. Med., 2003, vol. 163, pp. 1997–2004. doi: 10.1001/archinte.163.17.1997
  6. Ayadi W., Khabir A., Hadhri-Guiga B., Fki L., Toumi N., Siala W., Charfi S., Fendri A., Makni H., Boudawara T., Ghorbel A., Gargouri A., Jlidi R., Gargouri R., Busson P., Drira M., Daoud J., Frikha M., Hammami A., Karray-Hakim H. North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance. Bull. Cancer, 2010, vol. 97, pp. 475–482. doi: 10.1684/bdc.2010.1090
  7. Balfour H.H. Jr, Holman C.J., Hokanson K.M., Lelonek M.M., Giesbrecht J.E., White D.R., Schmeling D.O., Webb C.H., Cavert W., Wang D.H., Brundage R.C. A prospective clinical study of Epstein–Barr virus and host interactions during acute infectious mononucleosis. J. Infect. Dis., 2005, vol. 192, pp. 1505–1512. doi: 10.1086/491740
  8. Blake S.M., Eliopoulos A.G., Dawson C.W., Young L.S. The transmembrane domains of the EBV-encoded latent membrane protein 1 (LMP1) variant CAO regulate enhanced signalling activity. Virology, 2001, vol. 282, pp. 278–287. doi: 10.1006/viro.2001.0828
  9. Botezatu I.V., Kondratova V.N., Shelepov V.P., Lichtenstein A.V. DNA melting analysis: application of the “open tube” format for detection of mutant KRAS. Anal. Biochem., 2011, vol. 419, pp. 302–308. doi: 10.1016/j.ab.2011.08.015
  10. Cederberg L.E., Rabinovitch M.D., Grimm-Geris J.M., Schmeling D.O., Filtz E.A., Condon L.M., Balfour H.H.Jr. Epstein–Barr virus DNA in parental oral secretions: a potential source of infection for their young children. Clin. Infect. Dis., 2018. doi: 10.1093/cid/ciy464
  11. Chang C.M., Yu K.J., Mbulaiteye S.M., Hildesheim A., Bhatia K. The extent of genetic diversity of Epstein–Barr virus and its geographic and disease patterns: a need for reappraisal. Virus Res., 2009, vol. 143, pp. 209–221. doi: 10.1016/j.virusres.2009.07.005
  12. Dawson D.R., Wang C., Danaher R.J., Lin Y., Kryscio R.J., Jacob R.J., Miller C.S. Salivary levels of Epstein–Barr virus DNA correlate with subgingival levels, not severity of periodontitis. Oral Dis., 2009, vol. 15, pp. 554–559. doi: 10.1111/j.16010825.2009.01585.x
  13. 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, vol. 63, pp. 2982–2989.
  14. Dunmire S.K., Hogquist K.A., Balfour H.H. Infectious Mononucleosis. Curr. Top. Microbiol. Immunol., 2015, vol. 390, pp. 211–240. doi: 10.1038/cti.2015.1
  15. 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, vol. 261, pp. 79–95. doi: 10.1006/viro.1999.9855
  16. Farrell P.J. Signal transduction from the Epstein–Barr virus LMP-1 transforming protein. Trends Microbiol., 1998, vol. 6, pp. 175–177.
  17. Feederle R., Klinke O., Kutikhin A., Poirey R., Tsai M.H., Delecluse H.J. Epstein–Barr virus: from the detection of sequence polymorphisms to the recognition of viral types. Curr. Top. Microbiol. Immunol., 2015, vol. 390, pp. 119–148. doi: 10.1007/978-3319-22822-8_7
  18. Gantuz M., Lorenzetti M.A., Chabay P.A., Preciado M.V. A novel recombinant variant of latent membrane protein 1 from Epstein Barr virus in Argentina denotes phylogeographical association. PLoS One, 2017, vol. 12: e0174221. doi: 10.1371/journal.pone.0174221
  19. Gerber P., Walsh J.H., Rosenblum E.N., Purcell R.H. Association of EB-virus infection with the post-perfusion syndrome. Lancet, 1969, vol. 1, pp. 593–595.
  20. Gurtsevitch V.E., Iakovleva L.S., Shcherbak L.N., Goncharova E.V., Smirnova K.V., Diduk S.V., Kondratova V.N., Maksimovich D.M., Lichtenstein A.V., Seniuta N.B. The LMP1 oncogene sequence variations in patients with oral tumours associated or not associated with the Epstein–Barr. Mol. Biol., 2013, vol. 47, pp. 987–995.
  21. Hadinoto V., Shapiro M., Sun C.C., Thorley-Lawson D.A. The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output. PLoS Pathog., 2009, vol. 5: e1000496. doi: 10.1371/journal.ppat.1000496
  22. Hahn P., Novikova E., Scherback L., Janik C., Pavlish O., Arkhipov V., Nicholls J., Muller-Lantzsch N., Gurtsevitch V., Grasser F.A. The LMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion. Int. J. Cancer., 2001, vol. 91, pp. 815–821.
  23. Hu L., Troyanovsky B., Zhang X., Trivedi P., Ernberg I., Klein G. Differences in the immunogenicity of latent membrane protein 1 (LMP1) encoded by Epstein–Barr virus genomes derived from LMP1-positive and -negative nasopharyngeal carcinoma. Cancer Res., 2000, vol. 60, pp. 5589–5593.
  24. Hu L.F., Chen F., Zheng X., Ernberg I., Cao S.L., Christensson B., Klein G., Winberg G. Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1. Oncogene, 1993, vol. 8, pp. 1575–1583.
  25. Huen D.S., Henderson S.A., 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, vol. 10, pp. 549–560.
  26. Kanai K., Satoh Y., Saiki Y., Ohtani H., Sairenji T. Difference of Epstein–Barr virus isolates from Japanese patients and African Burkitt’s lymphoma cell lines based on the sequence of latent membrane protein 1. Virus Genes, 2007, vol. 34, pp. 55–61. doi: 10.1007/s11262-006-0010-y
  27. 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. USA, 1993, vol. 90, pp. 9150–9154.
  28. Kulwichit W., Edwards R.H., Davenport E.M., Baskar J.F., 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. USA, 1998, vol. 95, pp. 11963–11968.
  29. Laichalk L.L., Hochberg D., Babcock G.J., Freeman R.B., Thorley-Lawson D.A. The dispersal of mucosal memory B cells: evidence from persistent EBV infection. Immunity, 2002, vol. 16, pp. 745–754.
  30. Lawrence J.B., Villnave C.A., Singer R.H. Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell, 1988, vol. 52, pp. 51–61.
  31. Li H.P., Chang Y.S. Epstein–Barr virus latent membrane protein 1: structure and functions. J. Biomed. Sci., 2003, vol. 10, pp. 490–504. doi: 10.1159/000072376
  32. Lo Y.M., Chan L.Y., Lo K.W., Leung S.F., Zhang J., Chan A.T., Lee J.C., Hjelm N.M., Johnson P.J., Huang D.P. Quantitative analysis of cell-free Epstein–Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res., 1999, vol. 59, pp. 1188–1191.
  33. Miller W.E., Edwards R.H., Walling D.M., Raab-Traub N. Sequence variation in the Epstein–Barr virus latent membrane protein 1. J. Gen. Virol., 1994, vol. 75 (pt. 10), pp. 2729–2740. doi: 10.1099/0022-1317-75-10-2729
  34. Moorthy R.K., Thorley-Lawson D.A. All three domains of the Epstein–Barr virus-encoded latent membrane protein LMP-1 are required for transformation of rat-1 fibroblasts. J. Virol., 1993, vol. 67, pp. 1638–1646.
  35. Namikawa T., Fujisawa K., Munekage E., Munekage M., Oki Y., Maeda H., Kitagawa H., Ueta H., Kobayashi M., Hanazaki K. Epstein–Barr virus-associated early gastric carcinoma with lymphoid stroma, accompanied with lymph node metastasis. Mol. Clin. Oncol., 2018, vol. 8, pp. 561–566. doi: 10.3892/mco.2018.1567
  36. Neves M., Marinho-Dias J., Ribeiro J., Sousa H. Epstein–Barr virus strains and variations: geographic or disease-specific variants? J. Med. Virol., 2017, vol. 89, pp. 373–387. doi: 10.1002/jmv.24633
  37. Rickinson A.B., Long H.M., Palendira U., Munz C., Hislop A.D. Cellular immune controls over Epstein–Barr virus infection: new lessons from the clinic and the laboratory. Trends Immunol., 2014, vol. 35, pp. 159–169. doi: 10.1016/j.it.2014.01.003
  38. Rickinson A.B., Moss D.J. Human cytotoxic T lymphocyte responses to Epstein–Barr virus infection. Annu. Rev. Immunol., 1997, vol. 15, pp. 405–431. doi: 10.1146/annurev.immunol.15.1.405
  39. Saechan V., Settheetham-Ishida W., Kimura R., Tiwawech D., Mitarnun W., Ishida T. Epstein–Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups. J. Gen. Virol., 2010, vol. 91, pp. 2054–2061. doi: 10.1099/vir.0.021105-0
  40. Santpere G., Darre F., Blanco S., Alcami A., Villoslada P., Mar A.M., Navarro A. Genome-wide analysis of wild-type EpsteinBarr virus genomes derived from healthy individuals of the 1,000 Genomes Project. Genome Biol. Evol., 2014, vol. 6, pp. 846–860. doi: 10.1093/gbe/evu054
  41. Senyuta N., Yakovleva L., Goncharova E., Scherback L., Diduk S., Smirnova K., Maksimovich D., Gurtsevitch V. Epstein–Barr virus latent membrane protein 1 polymorphism in nasopharyngeal carcinoma and other oral cavity tumors in Russia. J. Med. Virol., 2014, vol. 86, pp. 290–300. doi: 10.1002/jmv.23729
  42. Tzellos S., Farrell P.J. Epstein–Barr virus sequence variation-biology and disease. Pathogens, 2012, vol. 1, pp. 156–174. doi: 10.3390/pathogens1020156
  43. Weiss L.M., Gaffey M.J., Chen Y.Y., Frierson H.F.Jr. Frequency of Epstein–Barr viral DNA in “Western” sinonasal and Waldeyer’s ring non-Hodgkin’s lymphomas. Am. J. Surg. Pathol., 1992, vol. 16, pp. 156–162.
  44. Wu L.Y., Cheng J., Lu Y., Zhou Z.Y., Saku T. Epstein–Barr virus infection in benign lymphoepithelial lesions with malignant transformation of salivary glands. Zhonghua Kou Qiang Yi Xue Za Zhi, 2004, vol. 39, pp. 291–293.
  45. Young L.S., Rickinson A.B. Epstein–Barr virus: 40 years on. Nat. Rev. Cancer, 2004, vol. 4, pp. 757–768. doi: 10.1038/nrc1452

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Copyright (c) 2020 Gurtsevitch V.E., Smirnova K.V., Botezatu I.V., Dushenkina T.E., Lubenskaya A.K., Dubar E., Senyuta N.B., Lichtenstein A.V., Petrov S.V.

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