THE EFFECTIVENESS OF DIFFERENT REGIMENS OF THERAPY IN PATIENTS WITH CHRONIC FORMS OF EPSTEINBARR VIRUS INFECTION

Liadova T. I., Volobueva O. V., Gamilovska A. P., Pavlikova K. V

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Chronic Epstein-Barr virus infection is characterized by the polymorphism of clinical manifestations and changes affecting all parts of the immune system, the violation of which are combined. The absence of effective schemes for the therapy of EBV infection is the basis for investigating the effectiveness of new immunotropic drugs that would eliminate the persistent virus and lead to a prolonged remission. Aim of research. To research the effectiveness of the allokin-alpha and the viferon in the correction of immune disorders in patients with chronic forms of EBV infection (HEBV). Object and methods. The material for the study was the serum of patients with HEBV infection, which was obtained during the period of the disease. Blood for research was collected from the elbow vein in the amount of 10 ml in a sterile Ependorf tube. Specific antiviral antibodies (VCA-IgM, EA-IgM and EBNA-IgG) in serum were determined by the solid-phase enzyme-linked immunosorbent assay (ELISA) with production sets “IBL” (Germany) and “Vector-Best” (RF) according to the instructions given. Amplisence reagent kits (Russia) were used to detect the DNA of the EBV by polymerase chain reaction (PCR) with reverse transcription with hybridization and fluorescence detection of amplification products. The isolation of the DNA from the specimens was carried out using a kit for DNA extraction by the firm Miniprep (Sillex M, Russia) using the method of sorption of DNA on sorbent by Voom R et al., 1990. The serum concentrations of the cytokins: IL-lβ, TNF-α, IL-6, IL-2, IL-4, IL-10 were determined using the test systems of the Protein Contour (St. Petersburg, Russia) using the manufacturer’s instructions using solid phase immunoassay (ELISA). The results of the research were processed by the method of variation and correlation statistics using the program “Statistica 10.0 for Windows”. As a result of the study, it was found that changes in the system of the cellular and humoral of immunity were revealed in patients with CEBV and the diverse direction of the immune response. The revealed changes in immune parameters indicate the formation of secondary cell immune imbalance, activation of the humoral link, and the change in the balance of immunoregulatory mediators towards Th2. Reactivation of HEBV is characterized by an increase in the number of cells with killer activity: mature T-lymphocytes (CD3+), cytotoxic T-suppressor cells (CD8+), cells expressing the activation marker CD25+ (IL-2 receptor) and a CD4+/CD8+ ratio. Appointment of immunomodulatory drugs allokine-alpha (alloferon) and the Viferon (recombinant interferon α2β) in combination with valaciclovir leads to a positive dynamics of immunological parameters as compared to the indicators of patients with baseline therapy, manifested by increased proliferative response, decreased levels of inflammatory and antiinflammatory cytokines and decreased levels Indicators characterizing the humoral response (CIC, Ig M, Ig G).

chronic Epstein-Barr viral infection, immune response, cytokines, antiviral therapy

• Vozianova ZhI, Hley AI. Infektsiyniy mononukleoz yak polietiolohichne zakhvoryuvannya. Suchasni infektsiyi. 2004;2:37-41. [in Ukrainian].
• Drutskaya MS, Belousov PV, Nedospasov SA. Vrozhdennoye raspoznavaniye virusov. Molekulyarnaya biologiya. 2011;45(1):7-19. [in Russian].
• Isakov VA, Arkhipova YeI, Isakov DV. Gerpesvirusnyye infektsii cheloveka: rukovodstvo dlya vrachey. SPb.; 2006. 303 s. [in Russian].
• Prokhorova NA, Volchkova YeV, Mikhaylovskaya GV. Klinicheskoye znacheniye molekulyarno-geneticheskikh i serologicheskikh issledovaniy v diagnostike infektsionnogo mononukleoza. Infektsionnyye bolezni. 2008;6(2):17-20. [in Russian].
• Cen О, Longnecker R. Latent Membrane Protein 2 (LMP2). Current topics in microbiology and immunology. 2015;391:151-80. DOI: 10.1007/978-3-319-22834-1_5
• Fukuda M, Kawaguchi Y. Role of the immunoreceptor tyrosine-based activation motif of latent membrane protein 2A (LMP2A) in EpsteinBarr virus LMP2A-induced cell transformation. Journal of Virology. 2014 May;88(9):5189-94. DOI: 10.1128/JVI.03714-13
• Griffin BD, Gram AM, Mulder A, Van Leeuwen D, Claas FH, Wang F, et al. BILF1 evolved to downregulate cell surface display of a wide range of HLA class I molecules through their cytoplasmic tail. Journal of Immunology. 2013 Feb 15;190(4):1672-84. DOI: 10.4049/jimmunol.1102462
• Thorley-Lawson DA, Hawkins JB, Tracy SI, Shapiro M. The pathogenesis of Epstein-Barr virus persistent infection. Current opinion in virology. 2013 Jun;3(3):227-32. DOI: 10.1016/j.coviro.2013.04.005
• Chang CM, Yu KJ, Mbulaiteye SM, Hildesheim A, Bhatia K. The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: a need for reappraisa. Virus Research. 2009 Aug;143(2):209-21. DOI: 10.1016/j.virusres.2009.07.005
• Bell MJ, Brennan R, Miles JJ, Moss DJ, Burrows JM, Burrows SR. Widespread sequence variation in Epstein-Barr virus nuclear antigen 1 influences the antiviral T cell response. Journal of Infection Diseases. 2008 Jun 1;197(11):1594-7. DOI: 10.1086/587848

«Bulletin of problems biology and medicine» Issue 1 Part 2 (143), 2018 year, 151-157 pages, index UDK 616.98:578.825:612.017:575.22

10.29254/2077-4214-2018-1-2-143-151-157