DOI: https://doi.org/10.20535/ibb.2017.1.1.112852

Study of Antiviral Activity of Recombinant Human Interleukin-7 with Various Experimental Models of Hepatitis C Viral Infection

Yulia I. Porva, Svitlana L. Rybalko, Svitlana T. Dyadyun, Tetiana M. Lutsenko, Alexander Yu. Galkin, Yanina A. Poholenko, Oksana B. Gorbatyuk

Abstract


Background. Interleukin-7 (IL-7) is one of the most important regulatory cytokine of immune system. Given the ability of IL-7 to the modulation of T- and B-cell responses and T-cell homeostasis we may assume that IL-7 not only has the ability to influence the formation of specific immunity and immunodeficiency state, but also inhibit the reproduction of viruses, including hepatitis C virus (HCV).

Objective. Study of antiviral activity of recombinant human IL-7 (rIL-7) with experimental models of viral hepatitis C infection in vitro on sensitive virus epithelial and lymphoid cells.

Methods. We have used the following inoculated cell cultures: Jurkat, rat neurinoma of gasserian ganglion and bovine kidney. As used surrogate HCV we used virus of bovine diarrhea. To study the antiviral activity different concentrations of rIL-7 were injected into the cell culture, producing HCV, and determined virus load. Also we have performed cytological analysis of cells and determined its proliferative activity under influence of rIL-7.

Results. It has been shown that rIL-7 inhibits surrogate HCV reproduction in in vitro conditions (SS50 – 3 mg/ml, ED50 – 4.7 ng/ml, IS – 640). Highest proliferation of intact T-cells is determined at rIL-7 doses 0.3 mg/m and 0.025 mg/ml. rIL-7 affected HCV infected cells differently: during the first 3 days the number of cells decreased or did not change, and after 2–3 weeks the number of cells increased almost 2 times. When we injected rIL-7 with dose of 6 mg/ml within 3 days we obtained 89% viral inhibition at the 3rd day and 100 % at the 4th day; using the dose of rIL-7 0.3 mg/ml the inhibition on the 4th day was 100 %; using dose of rIL-7 1.5 mg/ml the inhibition settled at 55 % for 4 days.

Conclusions. As a result of the studies directed towards determining the effect of rIL-7 on surrogate HCV reproduction, HCV cDNA producing transfected human T-cells Jurkat, it was showed that rIL-7 effectively inhibits virus reproduction.


Keywords


Human interleukin-7 recombinant; Hepatitis C virus; Antiviral activity; Viral load

References


Fry TJ, Maskall CL. Interleukin-7: from bench to clinic. Blood. 2002 Jun 1;99(11):3892-3894. DOI 10.1182/blood.V99.11.3892

Bolotin E, Annett G, Parkman R, Weinberg K. Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. Bone Marrow Transplant. 1999 Apr;23(8):783-8.

Rosenberg SA, Sportès C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, et al. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006 May-Jun;29(3):313-9. DOI 10.1097/01.cji.0000210386.55951.c2

De Saint-Vis B, Fugier-Vivier I, Massacrier C, Gaillard C, Vanbervliet B, Aït-Yahia S, et al. The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. J Immunol. 1998 Feb 15;160(4):1666-76.

Sorg RV, McLellan AD, Hock BD, Fearnley DB, Hart DN. Human dendritic cells express functional interleukin-7. Immunobiology. 1998 Mar;198(5):514-26. DOI 10.1016/S0171-2985(98)80075-2

Clarke D, Katoh O, Gibbs RV, Griffiths SD, Gordon MY. Interaction of interleukin-7 (IL-7) with glycosaminoglycans and its biological relevance. Cytokine. 1995 May;7(4):325-30. DOI 10.1006/cyto.1995.0041

Kimura K, Matsubara H, Sogoh S, Kita Y, Sakata T, Nishitani Y, et al. Role of glycosaminoglycans in the regulation of T cell proliferation induced by thymic stroma-derived T cell growth factor. J Immunol. 1991 Apr 15;146(8):2618-24.

Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID), Nature. 1995 Sep 7;377(6544):65-8. DOI 10.1038/377065a0

Russell S, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, et al. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995 Nov 3;270(5237):797-800.

Fry T, Mackall C. Interleukin-7: master regulator of peripheral T-cell homeostasis? Trends Immunol. 2001 Oct;22(10):564-71.

Hardy R, Carmack CE, Shinton SA, Kemp JD, Hayakawa K. Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med. 1991 May 1;173(5):1213-25.

Morrissey PJ, Conlon P, Braddy S, Williams DE, Namen AE, Mochizuki DY. Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation. J Immunol. 1991 Mar 1;146(5):1547-52.

Lynch D, Namen A, Miller R. In vivo evaluation of the effects of interleukins 2, 4 and 7 on enhancing the immunotherapeutic efficacy of anti-tumor cytotoxic T lymphocytes. Eur J Immunol. 1991 Dec;21(12):2977-85. DOI 10.1002/eji.1830211212

Plumb AW, Patton DT, Seo JH, Loveday EK, Jean F, Ziegler SF, et al. Interleukin-7, but not thymic stromal lymphopoietin, plays a key role in the T cell response to influenza A virus. PLoS One. 2012;7(11):e50199. DOI 10.1371/journal.pone.0050199

Larrubia J, Lokhande MU, García-Garzón S, Miquel J, González-Praetorius A, Parra-Cid T, et al. Persistent hepatitis C virus (HCV) infection impairs HCV-specific cytotoxic T cell reactivity through Mcl-1/Bim imbalance due to CD127 down-regulation. J Viral Hepat. 2013 Feb;20(2):85-94. DOI 10.1111/j.1365-2893.2012.01618.x

Hou L, Jie Z, Desai M, Liang Y, Soong L, Wang T, et al. Early IL-7 production by intrahepatic T cell is important for adaptive immune responses in viral hepatitis. J Immunol. 2013 Jan 15;190(2):621-9. DOI 10.4049/jimmunol.1201970

Blumkin VN, Zhdanov VM. The impact of viruses on the chromosome apparatus and cell division. Moscow: Medicina; 1973. 128 p.


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