Research of prevalence of polymorphism of the TLR 9 type gene in patients with infectious mononucleosis, caused by Epstein-Barr virus

Authors

DOI:

https://doi.org/10.15587/2519-4798.2017.113311

Keywords:

Epstein-Barr virus, Toll-like receptors, polymorphism, prevalence

Abstract

There was studied the prevalence of -1486 T/C polymorphism of TLR-9 gene in 52 patients with infectious mononucleosis (IM), caused by Epstein-Barr virus. Three main genotypes of - 1486 T/C of TLR-9 gene: TT, TC, CC were identified based on obtained results. The study of the frequency of appearance of separate genotypes in patients with IM revealed the dominance of CC and TT genotypes compared with the control group. The study of the distribution frequency of -1486 T/C-polymorphism of TLR-9 gene for different genotypes demonstrated the specificity of CC genotype changes in patients with IM and the absence of such changes for TT and TC genotypes.

Aim of research. The study of the frequency of - 1486 T/C polymorphism of TLR-9 gene in patients with IM, caused by Epstein-Barr virus.

Materials and methods. The study for determining -1486 T / C polymorphism of TLR-9 gene was realized in 52 patients with IM. Among them women - 31 (59,6 %), men - 21 (40,4 %) in the age diapason from 18 to 34 years. The control group for studying the prevalence of - 1486 T/Cpolymorphism of TLR-9 gene consisted of 40 healthy donors. The mean age 24,2 ± 2,4 years, from 18 to 44 years.

For revealing DNA of EBV by the method of the reverse transcription of PCR with hybridization-fluorescent detection of amplification products, sets of reagents Amplisens (Russia) were used. The polymorphic zone - 1486 T / C, rs187084 of TLR9 gene was used by PCR amplification in real time by determining the length of restrictive fragments of PCR using Ncol restrictive fragment and oligonucleotide primers.

Results. The analysis of results of - 1486 T/C polymorphism of TLR-9 gene allowed to identify three main genotypes - TT, TC, CC. The study of the frequency of separate genotypes detection allowed to establish the prevalence of CC and TT genotypes compared with the heterozygotic TC genotype. The study of the distribution frequency of -1486 T/C-polymorphism of TLR-9 gene for different genotypes demonstrated the specificity of CC genotype changes in patients with IM and the absence of such changes for TT and TC genotypes.

Our research established the correlation between - 1486 TLR-9 C/Cpolymorphism with IM that proves the important role of mediated TLR signalization in the pathogenesis of EBV infection. The study of genes polymorphism among receptors that take part in recognizing a virus is necessary for determining the genetic background, connected with the infection risk, disease course and possible IM results. It allows to reveal risk groups among patients and to carry out the timely therapy.

Conclusions: 1. It was proved, that - 1486 T/C polymorphism of TLR-9 gene is detected reliably more often in patients with IM than in the control group.

2. The distribution of -1486 Т / С polymorphism of TLR-9 allowed to reveal the association of CC genotype with manifest forms of IM

Author Biography

Tatiana Liadova, V. N. Karazin Kharkov national university Svobody squ., 4, Kharkiv, Ukraine, 61022

Candidate of Medical Sciences, associate professor

Department of General and Clinical Immunology and Allergology

References

  1. Drutskaya, M. S., Belousov, P. V., Nedospasov, S. A. (2011). Vrozhdennoe raspoznavanie virusov. Molekulyarnaya biologiya, 25 (3), 7–19.
  2. Sha, Q., Truong-Tran, A. Q., Plitt, J. R., Beck, L. A., Schleimer, R. P. (2004). Activation of Airway Epithelial Cells by Toll-Like Receptor Agonists. American Journal of Respiratory Cell and Molecular Biology, 31 (3), 358–364. doi: 10.1165/rcmb.2003-0388oc
  3. Vaidya, S. A., Cheng, G. (2003). Toll-like receptors and innate antiviral responses. Current Opinion in Immunology, 15 (4), 402–407. doi: 10.1016/s0952-7915(03)00070-0
  4. Barton, G. M. (2007). Viral recognition by Toll-like receptors. Seminars in Immunology, 19 (1), 33–40. doi: 10.1016/j.smim.2007.01.003
  5. Kawai, T., Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology, 11 (5), 373–384. doi: 10.1038/ni.1863
  6. Sandor, F., Buc, M. (2005). Toll-like receptors. I. Structure, function and their ligands. Folia Biol (Praha), 51 (5), 148–157.
  7. Torres, S., Hernández, J. C., Giraldo, D., Arboleda, M., Rojas, M., Smit, J. M., Urcuqui-Inchima, S. (2013). Differential Expression of Toll-like Receptors in Dendritic Cells of Patients with Dengue during Early and Late Acute Phases of the Disease. PLoS Neglected Tropical Diseases, 7 (2), e2060. doi: 10.1371/journal.pntd.0002060
  8. Gibson, J., Gow, N., Wong, S. Y. C. (2010). Expression and Functions of Innate Pattern Recognition Receptors in T and B Cells. Immunology‚ Endocrine & Metabolic Agents in Medicinal Chemistry, 10 (1), 11–20. doi: 10.2174/187152210791171304
  9. Iskra, S., Kalla, M., Delecluse, H.-J., Hammerschmidt, W., Moosmann, A. (2010). Toll-Like Receptor Agonists Synergistically Increase Proliferation and Activation of B Cells by Epstein-Barr Virus. Journal of Virology, 84 (7), 3612–3623. doi: 10.1128/jvi.01400-09
  10. Bochud, P.-Y., Hersberger, M., Taffé, P., Bochud, M., Stein, C. M., Rodrigues, S. D. et. al. (2007). Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection. AIDS, 21 (4), 441–446. doi: 10.1097/qad.0b013e328012b8ac
  11. Vozianova, Zh. I., Hlei, A. I. (2004). Infektsiynyi mononukleoz yak polietyolohichne zakhvoriuvannia. Suchasni infektsyi, 2, 37–41.
  12. Thuong, N. T. T., Hawn, T. R., Thwaites, G. E., Chau, T. T. H., Lan, N. T. N., Quy, H. T. et. al. (2007). A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes and Immunity, 8 (5), 422–428. doi: 10.1038/sj.gene.6364405
  13. Carvalho, A., Cunha, C., Almeida, A. J., Osório, N. S., Saraiva, M., Teixeira-Coelho, M. et. al. (2011). The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma. Genes and Immunity, 13 (2), 197–201. doi: 10.1038/gene.2011.59
  14. Woehrle, T., Du, W., Goetz, A., Hsu, H.-Y., Joos, T. O., Weiss, M. et. al. (2008). Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans. Cytokine, 41 (3), 322–329. doi: 10.1016/j.cyto.2007.12.006
  15. Kijpittayarit, S., Eid, A. J., Brown, R. A., Paya, C. V., Razonable, R. R. (2007). Relationship between Toll-Like Receptor 2 Polymorphism and Cytomegalovirus Disease after Liver Transplantation. Clinical Infectious Diseases, 44 (10), 1315–1320. doi: 10.1086/514339
  16. Akin, E., McHugh, G. L., Flavell, R. A., Fikrig, E., Steere, A. C. (1999). The Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis. Infection and Immunity, 67 (1), 173–181.
  17. Bernardino, A. L. F., Myers, T. A., Alvarez, X., Hasegawa, A., Philipp, M. T. (2008). Toll-Like Receptors: Insights into Their Possible Role in the Pathogenesis of Lyme Neuroborreliosis. Infection and Immunity, 76 (10), 4385–4395. doi: 10.1128/iai.00394-08
  18. Salazar, J. C., Pope, C. D., Sellati, T. J., Feder, H. M., Kiely, T. G. et. al. (2003). Coevolution of Markers of Innate and Adaptive Immunity in Skin and Peripheral Blood of Patients with Erythema Migrans. The Journal of Immunology, 171 (5), 2660–2670. doi: 10.4049/jimmunol.171.5.2660
  19. Gaudreault, E., Fiola, S., Olivier, M., Gosselin, J. (2007). Epstein-Barr Virus Induces MCP-1 Secretion by Human Monocytes via TLR2. Journal of Virology, 81 (15), 8016–8024. doi: 10.1128/jvi.00403-07
  20. Fathallah, I., Parroche, P., Gruffat, H., Zannetti, C., Johansson, H., Yue, J. et. al. (2010). EBV Latent Membrane Protein 1 Is a Negative Regulator of TLR9. The Journal of Immunology, 185 (11), 6439–6447. doi: 10.4049/jimmunol.0903459
  21. Fiola, S., Gosselin, D., Takada, K., Gosselin, J. (2010). TLR9 Contributes to the Recognition of EBV by Primary Monocytes and Plasmacytoid Dendritic Cells. The Journal of Immunology, 185 (6), 3620–3631. doi: 10.4049/jimmunol.0903736
  22. Paradowska, E., Jabłońska, A., Studzińska, M., Skowrońska, K., Suski, P., Wiśniewska-Ligier, M. et. al. (2016). TLR9 -1486T/C and 2848C/T SNPs Are Associated with Human Cytomegalovirus Infection in Infants. PLOS ONE, 11 (4), e0154100. doi: 10.1371/journal.pone.0154100

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Published

2017-10-31

How to Cite

Liadova, T. (2017). Research of prevalence of polymorphism of the TLR 9 type gene in patients with infectious mononucleosis, caused by Epstein-Barr virus. ScienceRise: Medical Science, (10 (18), 24–28. https://doi.org/10.15587/2519-4798.2017.113311

Issue

No. 10 (18) (2017)

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Medical Science

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Copyright (c) 2017 Татьяна Ивановна Лядова

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