Mikrobiol. Z. 2018; 80(4):88-95.
doi: https://doi.org/10.15407/microbiolj80.04.088

Impaired up-Expression of pro-Oxidation Genes by Oligoribonucleotides
at Influenza А Virus Infection in vivo

Melnichuk N.S.1, Rybalko S.L.2, Tkachuk Z.Yu.1

1Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Akad. Zabolotny Str., Kyiv, 03680, Ukraine

2Gromashevsky Institute of Epidemiology and Infectious Diseases, NAMS of Ukraine
5 Amosov Str., Kyiv, 03038, Ukraine

Aim. Current research was aimed at study of the oligoribonucleotides effects on expression of the nos2, xdh, arg2 genes in mice lungs at influenza virus infection. Methods. To achieve this goal we applied a real-time polymerase chain reaction and lipid peroxidation assay. Results. In the present studies, we have found the mRNA up-expression of arg2, nos2, xdh after 48 h influenza virus infection. The oligoribonucleotides have been shown to impair the up-expression of nos2, xdh, arg2 genes induced by the influenza virus. They also decrease the level of lipid peroxidation products at influenza virus infection. Conclusions. Oligoribonucleotides normalize the overexpression of pro-oxidation genes induced by the influenza virus infection. By suppressing the up-regulation of these genes, oligoribonucleotides reduce the level of lipid peroxidation products at influenza virus infection. Impaired these genes overexpression at influenza virus infection can be one of elements of the mechanism action of the oligoribonucleotides as knew anti-influenza, anti-inflammation drug.

Keywords: oligoribonucleotides, influenza, expression of nos2, xdh, arg2 genes.

Full text (PDF, in English)

  1. Garten R.J., Davis C.T., Russell C.A., Shu, B. Lindstrom, S., Balish, A. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009; 325:197-201. https://doi.org/10.1126/science.1176225
  2. Cees J., Doelman A., Aalt B. Oxygen radicals in lung pathology. Free Rad. Biol. Med. 1991; 9:381-400.
  3. Akaike T. Role of free radicals in viral pathogenesis and mutation. Rev Med Virol. 2001; 11(2):87-101. https://doi.org/10.1002/rmv.303
  4. Perrone L.A., Belser J.A., Wadford D.A., Katz J.M., Tumpey T.M. Inducible Nitric Oxide Contributes to Viral Pathogenesis Following Highly Pathogenic Influenza Virus Infection in Mice. Infectious Diseases. 2013; 207(10):1576-1584. https://doi.org/10.1093/infdis/jit062
  5. Zou W.1., Chen D., Xiong M., Zhu J., Lin X., Wang L., et al. Insights into the increasing virulence of the swine-origin pandemic H1N1/2009 influenza virus. Sci Rep. 2013; 3:1601. https://doi.org/10.1038/srep01601
  6. Dawson T.C., Beck M.A., Kuziel W.A., Henderson F., Maeda N. Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am J Pathol. 2000; 156:1951-1959. https://doi.org/10.1016/S0002-9440(10)65068-7
  7. Uetani K.1., Der S.D., Zamanian-Daryoush M., de La Motte C., Lieberman B.Y., Williams B.R., Erzurum S.C. Role of Double-Stranded RNA-Activated Protein Kinase in Microbial Induction of Nitric Oxide Synthase1. Immunol. 2000; 165(2):988-996. https://doi.org/10.4049/jimmunol.165.2.988
  8. Akaike T.1., Ando M., Oda T., Doi T., Ijiri S., Araki S., Maeda H. Dependence on 02 Generation by Xanthine Oxidase of Pathogenesis of Influenza Virus Infection in Mice. J Clin Invest. 1990; 85(3):739-45. https://doi.org/10.1172/JCI114499
  9. Akaike T., Noguchi Y., Ijiri S., Setoguchi K., Suga M., Zheng Y.M., et al. Pathogenesis of influenza virusinduced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc. Natl. Acad. Sci. USA. 1996; 93:2448-53. https://doi.org/10.1073/pnas.93.6.2448
  10. Akaike T., Maeda H. Nitric oxide and virus infection. Immunology. 2000; 101:300-8. https://doi.org/10.1046/j.1365-2567.2000.00142.x
  11. Tkachuk Z. Multiantivirus Compound, Composition and Method for Treatment of Virus Diseases. U.S. Patent 20,120,232,129, 16 April 2013.
  12. Tkachuk Z.Y., Rybalko S.L., Zharkova L.D., Starostyla D.B. [Antiinfluenzal activity of drug Nuclex]. Rep. Natl. Acad. Sci. Ukr. 2010; 9:191-196. Ukrainian.
  13. Melnichuk N.S., Semernikova L.I., Tkachuk Z.Yu. Complexes of Oligoribonucleotides with D-mannitol inhibit hemagglutinin–glycan interaction and suppress influenza A virus H1N1 (A/FM/1/47) infectivity in vitro. Pharmaceuticals. 2017; 10(71):1-9.
  14. Tkachuk Z.Yu., Tkachuk V.V., Tkachuk L.V. The study on membrane-stabilizing and anti-inflammatory actions of yeast RNA in vivo and in vitro. Biopolym. Cell. 2006; 22(2):109-116. Ukrainian. https://doi.org/10.7124/bc.000723
  15. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001; 25:402-408. https://doi.org/10.1006/meth.2001.1262
  16. Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75.
  17. Asakawa T., Matsushita S. Thiobarbituric acid test for detecting lipid peroxides. Lipids. 1980; 14:401-406. https://doi.org/10.1007/BF02533425
  18. De Clercq, E. Human viral diseases: what is next for antiviral drug discovery? Curr. Opin. Virol. 2012; 2:572-579. https://doi.org/10.1016/j.coviro.2012.07.004
  19. Sgarbanti R., Amatore D., Celestino I., Marcocci M E., Fraternale A., Ciriolo M.R., et al. Intracellular Redox State as Target for Anti-Influenza Therapy: Are Antioxidants Always Effective? Curr Top Med Chem. 2014; 14(22):2529-2541. https://doi.org/10.2174/1568026614666141203125211
  20. Nikam S.V., Nikam P.S., Chandrashekar M.R., Kalsad S.T., Jnaneshwara K.B. Role of lipid peroxidation, glutathione and antioxidant enzymes in H1N1 Influenza. Biomedical Research. 2010; 21(4):457-560.
  21. Lucas R.1., Czikora I., Sridhar S., Zemskov E.A., Oseghale A., Circo S., et al. Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury. Front Immunol. 2013; 4:228. https://doi.org/10.3389/fimmu.2013.00228
  22. Zelyoniy I.I., Tkachuk Z.Yu., Afonin D.N., Tiutiunnyk A. A. [Effect of Nuclex on the cytokine profile of patient with diabetes mellitus type 2 and neuropathic form of diabetic foot syndrome]. Natl. Acad. Med. Ukr. 2014; 20(2):240-245. Ukrainian.
  23. Tkachuk Z. Method of protecting erythricytes, in particular for improvement of blood cytopenia. U.S. Patent 6,737,271. 26.03.2001.