Skip to main content
SpringerLink
Log in

The functional analysis of Epstein-Barr virus latent membrane proteins (LMP1) in patients with lymphoproliferative disorders

  • Published:
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) encoded by the LMP1 gene is a transmembrane protein, which can activate a number of cellular signal cascades and transcriptional factors leading to cell transformation. In the present study the sequencing of full-length LMP1 variants isolated from Russian patients with Hodgkin’s lymphoma (HL), non-Hodgkin’s lymphomas (NHL) and infectious mononucleosis (IM) has been carried out. The phylogenetic analysis of the obtained sequences revealed dominance of the LMP1 variants belonging to proteins of the low-divergent group LMP1-B95.8b characterized by minimal set of mutations. Investigation of biological properties in the Russian representatives of this group revealed that expression of the studied LMP1 variants in embryonic kidney (HEK) 293 cells was accompanied by an insignificant increase in activation of the transcriptional factor NF-κB and had minor influence on activation of the transcriptional factor AP-1. It was also detected that all investigated low-divergent LMP1 variants expressed in Rat-1 cells caused activation of inducible NO-synthase (iNOS) and intracellular production of nitric oxide (NO). At the same time the level of NO accumulation was lower than that induced by the low-transforming prototype variant LMP1-B95.8. The data obtained indicate that the LMP1 variants, which are the most common among Russian patients with EBV-associated lymphoproliferative diseases, are characterized by minimum number of mutations and rather low ability to activate basic cellular signaling pathways regardless the nature of pathological process, benign (IM) or malignant (HL, NHL). It is suggested that in addition to the modest activation of NF-κB and iNOS induction by LMP1 other factors are involved in the cell transformation process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CTAR1:

C-terminal activating region 1

CTAR2:

C-terminal activating region 2

Dex:

dexamethasone

EBV:

Epstein-Barr Virus

HL:

Hodgkin’s lymphoma

IM:

infectious mononucleosis

iNOS:

inducible Nitric Oxide Synthase

LMP1:

latent membrane protein 1

NHL:

non-Hodgkin’s lymphomas

References

  1. Kaye, K.M., Izumi, K.M., and Kieff, E., Proc. Natl. Acad. Sci. USA, 1993, vol. 90, pp. 9150–9154.

    Article  CAS  Google Scholar 

  2. Moorthy, R.K. and Thorley-Lawson, D.A., J. Virol., 1993, vol. 67, pp. 1638–1646.

    CAS  Google Scholar 

  3. Kulwichitm, W., Edwards, R.H., Davenport, E.M., Baskar, J.F., Godfrey, V., and Raab-Traub, N., Proc. Natl. Acad. Sci. USA, 1998, vol. 95, pp. 11963–11968.

    Article  Google Scholar 

  4. Fennewald, S., van Santen, V., and Kieff, E., J. Virol., 1984, vol. 51, pp. 411–419.

    CAS  Google Scholar 

  5. Cahir-McFarland, E.D., Izumi, K.M., and Mosialos, G., Oncogene, 1999, vol. 18, pp. 6959–6964.

    Article  CAS  Google Scholar 

  6. Wu, L., Nakano, H., and Wu, Z., J. Biol. Chem., 2006, vol. 281, pp. 2162–2169.

    Article  CAS  Google Scholar 

  7. Eliopoulos, A.G. and Young, L.S., Oncogene, 1998, vol. 16, pp. 1731–1742.

    Article  CAS  Google Scholar 

  8. Eliopoulos, A.G., Blake, S.M., Floettmann, J.E., Rowe, M., and Young, L.S., J. Virol., 1999, vol. 73, pp. 1023–1025.

    CAS  Google Scholar 

  9. Lam, N. and Sagden, B., Cell Signal., 2003, vol. 15, pp. 9–16.

    Article  CAS  Google Scholar 

  10. Dawson, C.W., Tramountanis, G., Eliopoulos, A.G., and Young, L.S., J. Biol.Chem., 2003, vol. 278, pp. 3694–3704.

    Article  CAS  Google Scholar 

  11. Coffin, W.F., Erickson, K.D., Hoedt-Miller, M., and Martin, J.M., Oncogene, 2001, vol. 20, pp. 5313–5330.

    Article  CAS  Google Scholar 

  12. Walling, D.M., Shebib, N., Weaver, S.C., Nichols, C.M., Flaitz, C.M., and Webster-Cyriaque, J., J. Infect. Dis., 1999, vol. 179, pp. 763–764.

    Article  CAS  Google Scholar 

  13. Hu, L.F., Zabarovsky, E.R., Chen, F., Cao, S.L., Emberg, I., Klein, G., and Winberg, G., J. Gen. Virol., 1991, vol. 72, pp. 2399–2409.

    Article  CAS  Google Scholar 

  14. Edwards, R.H., Seiller-Moiseiwitsch, F., and Raab-Traub, N., Virology, 1999, vol. 261, pp. 79–95.

    Article  CAS  Google Scholar 

  15. Nitta, T., Chiba, A., Yamamoto, N., and Yamaoka, S., Cell. Signal., 2004, vol. 16, pp. 1071–1081.

    CAS  Google Scholar 

  16. Pavlish, O.A., Diduk, S.V., Smirnova, K.V., Scherbak, L.N., Goncharova, E.V., Shalginskikh, N.A., Arkhipov, V.V., Kichigina, M.Yu., Stepina, V.N., Belousova, N.V., Osmanov, E.A., Yakovleva, L.S., and Gurtsevitch, V.E., Vopr. Virusol., 2008, vol. 53, pp. 10–16.

    CAS  Google Scholar 

  17. Sandvej, K., Peh, S.C., Andresen, B.S., and Pallesen, G., Blood, 1994, vol. 84, pp. 4053–4060.

    CAS  Google Scholar 

  18. Nathan, C., FASEB. J., 1992, vol. 6, pp. 3051–3064.

    CAS  Google Scholar 

  19. Moncada, S., Palmer, R.M., and Higgs, E.A., Pharmacol. Rev., 1991, vol. 43, pp. 109–142.

    CAS  Google Scholar 

  20. Yu, J.S., Tsai, H.S., Wu, C.C., Weng, L.P., Li, H.P., Chung, P.J., and Chang, Y.S., Oncogene, 2002, vol. 21, pp. 8047–8061.

    Article  CAS  Google Scholar 

  21. Edwards, R.H., Seiller-Moiseiwitsch, F., and Raab-Traub, N., Virology, 1999, vol. 261, pp. 79–95.

    Article  CAS  Google Scholar 

  22. Sandvej, K., Gratama, J.W., Munch, M., Zhou, X.G., Bolhuis, R.L., Andresen, B.S., Gredersen, N., and Hamilton-Dutoit, S., Blood, 1997, vol. 90, pp. 323–330.

    CAS  Google Scholar 

  23. Edwards, R.H., Sitki-Green, D., Moore, D.T., and Raab-Traub, N., J. Virol., 2004, vol. 78, pp. 868–881.

    Article  CAS  Google Scholar 

  24. Thomson, J.D., Gibson, T.J., Plewniak, F., Jeanmougin, F., and Higgins, D.G., Nucl. Acid. Res., 1997, vol. 24, pp. 4876–4882.

    Article  Google Scholar 

  25. Saitou, N. and Nei, M., Mol. Biol. Evol., 1987, vol. 4, pp. 406–425.

    CAS  Google Scholar 

  26. Van de Peer, Y. and de Wachter, R., Comput. Applic. Biosci., 1994, vol. 10, pp. 569–570.

    Google Scholar 

  27. Felsenstein, J., Evolution, 1985, vol. 39, pp. 783–791.

    Article  Google Scholar 

  28. Bradford, M.M., Anal. Biochem., 1976, vol. 72, pp. 248–254.

    Article  CAS  Google Scholar 

  29. Tang, W., Pavlish, O.A., Spiegelman, V.S., Parkhitko, A.A., and Fuchs, S.Y., J. Biol. Chem., 2003, vol. 278, pp. 48942–48949.

    Article  CAS  Google Scholar 

  30. Fielding, C.A., Sandvej, K., Mehl, A., Brennan, P., Jones, M., and Rowe, M., (2001) J. Virol., 2001, vol. 75, pp. 9129–9141.

    Article  CAS  Google Scholar 

  31. Diduk, S.V., Smirnova, K.V., Pavlish, O.A., and Gurtsevitch, V.E., Biochemistry (Moscow), 2008, vol. 73, pp. 1414–1421.

    Article  Google Scholar 

  32. Ma, N., Kawanishi, M., Hiraku, Y., Murata, M., Huang, G.W., Huang, Y., Luo, D.Z., Mo, W.G., Fukui, Y., and Kawanishi, S., Int. J. Cancer, 2008, vol. 122, pp. 2517–2525.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse 24, Moscow, Russia

    K. V. Smirnova, S. V. Diduk & V. E. Gurtsevitch

Authors
  1. K. V. Smirnova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. V. Diduk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. E. Gurtsevitch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. E. Gurtsevitch.

Additional information

Original Russian Text © K.V. Smirnova, S.V. Diduk, V.E. Gurtsevitch, 2010, published in Biomeditsinskaya Khimiya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smirnova, K.V., Diduk, S.V. & Gurtsevitch, V.E. The functional analysis of Epstein-Barr virus latent membrane proteins (LMP1) in patients with lymphoproliferative disorders. Biochem. Moscow Suppl. Ser. B 4, 386–394 (2010). https://doi.org/10.1134/S1990750810040116

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990750810040116

Keywords

Search

Navigation