Skip to main content

Advertisement

Log in

Analysis of Immunogenicity of Intracellular CTAR Fragments of Epstein—Barr Virus Latent Phase Protein LMP1

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Intracellular fragments of latent phase protein LMP1 of Epstein—Barr virus, denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to the transforming potential of the virus. Generation of recombinant proteins CTAR1/2/3 is expected to yield more ample data on functional and immunogenic characteristics of LMP1. We created genetic constructs for prokaryotic expression of LMP1 CTAR fragments and selected optimal conditions for their production and purification. Using a new library of LMP1 CTAR fragments, we carried out epitope mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of CTAR elements comparable with that of full-length protein

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Smirnova KV, Diduk SV, Senyuta NB, Gurtsevitch VE. Molecular biological properties of the Epstein—Barr virus LMP1 gene: structure, function and polymorphism. Vopr. Virusol. 2015;60(3):5-13.

    CAS  PubMed  Google Scholar 

  2. Aga M, Bentz GL, Raffa S, Torrisi MR, Kondo S, Wakisaka N, Yoshizaki T, Pagano JS, Shackelford J. Exosomal HIF1a supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes. Oncogene. 2014;33(37):4613-4622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Balandraud N, Roudier J, Roudier C. Epstein—Barr virus and rheumatoid arthritis. Autoimmun. Rev. 2004;3(5):362-367.

    Article  CAS  PubMed  Google Scholar 

  4. Casiraghi C, Márquez AC, Shanina I, Horwitz MS. Latent virus infection upregulates CD40 expression facilitating enhanced autoimmunity in a model of multiple sclerosis. Sci. Rep. 2015;5:13995.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Edwards RH, 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.

    Article  CAS  PubMed  Google Scholar 

  6. Gabibov AG, Belogurov AA Jr, Lomakin YA, Zakharova MY, Avakyan ME, Dubrovskaya VV, Smirnov IV, Ivanov AS, Molnar AA, Gurtsevitch VE, Diduk SV, Smirnova KV, Avalle B, Sharanova SN, Tramontano A, Friboulet A, Boyko AN, Ponomarenko NA, Tikunova NV. Combinatorial antibody library from multiple sclerosis patients reveals antibodies that crossreact with myelin basic protein and EBV antigen. FASEB J. 2011;25(12):4211-4221.

    Article  CAS  PubMed  Google Scholar 

  7. Izumi KM, Cahir McFarland ED, Riley EA, Rizzo D, Chen Y, Kieff E. The residues between the two transformation effector sites of Epstein—Barr virus latent membrane protein 1 are not critical for B-lymphocyte growth transformation. J. Virol. 1999;73(12):9908-9916.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Jha HC, Banerjee S, Robertson ES. The role of gammaherpesviruses in cancer pathogenesis. Pathogens. 2016;5(1):pii: E18. doi: https://doi.org/10.3390/pathogens5010018.

  9. Kang I, Quan T, Nolasco H, Park S., Hong MS, Crouch J, Pamer EG, Howe JG, Craft J. Defective control of latent Epstein—Barr virus infection in systemic lupus erythematosus. J. Immunol. 2004;172(2):1287-1294.

    Article  CAS  PubMed  Google Scholar 

  10. Lomakin YA, Zakharova MY, Stepanov AV, Dronina MA, Smirnov I.V, Bobik TV, Pyrkov AY, Tikunova NV, Sharanova SN, Boitsov VM, Vyazmin SY, Kabilov MR, Tupikin AE, Krasnov AN, Bykova NA, Medvedeva YA, Fridman MV, Favorov AV, Ponomarenko NA, Dubina MV, Boyko AN, Vlassov VV, Belogurov AA Jr, Gabibov AG. Heavy-light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation. Mol. Immunol. 2014;62(2):305-314.

  11. Mann KP, Staunton D, Thorley-Lawson DA. Epstein—Barr virus-encoded protein found in plasma membranes of transformed cells. J. Virol. 1985;55(3):710-720.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Souza TA, Stollar BD, Sullivan JL, Luzuriaga K, Thorley-Lawson DA. Peripheral B cells latently infected with Epstein—Barr virus display molecular hallmarks of classical antigen-selected memory B cells. Proc. Natl Acad. Sci. USA. 2005;102(50):18,093-18,098.

    Article  CAS  Google Scholar 

  13. Uchida J, Yasui T, Takaoka-Shichijo Y, Muraoka M, Kulwichit W, Raab-Traub N, Kikutani H. Mimicry of CD40 signals by Epstein—Barr virus LMP1 in B lymphocyte responses. Science. 1999;286:300-303.

    Article  CAS  PubMed  Google Scholar 

  14. Wang S, Xiong H, Yan S, Wu N, Lu Z. Identification and characterization of Epstein—Barr virus genomes in lung carcinoma biopsy samples by next-generation sequencing technology. Sci. Rep. 2016;6:26156. doi: https://doi.org/10.1038/srep26156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Young LS, Rickinson AB. Young LS, Rickinson AB. Epstein—Barr virus: 40 years on. Nat. Rev. Cancer. 2004;4(10):757-768.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. A. Belogurov Jr.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 163, No. 6, pp. 732-737, June, 2017

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lomakin, Y.A., Shmidt, A.A., Bobik, T.V. et al. Analysis of Immunogenicity of Intracellular CTAR Fragments of Epstein—Barr Virus Latent Phase Protein LMP1. Bull Exp Biol Med 163, 766–771 (2017). https://doi.org/10.1007/s10517-017-3899-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-017-3899-3

Key Words

Navigation