Biopolym. Cell. 1999; 15(4):314-318.
Viruses and Cell
The effect of trimeric 2',5'-oligoadenylic acid and its epoxyderivative on the human immunodeficiency virus reproduction and retroviruses reverse transcriptase activity
1Tkachuk Z. Yu., 2Rybalko S. L., 1Semernikova L. I., 1Tkachuk V. V., 3Zavelevich M. P., 1Tkachuk L. V., 4Mikhailopulo I. O., 1Matsuka G. Kh.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Gromashevsky L.V. Institute of Epidemiology and Infection Diseases, AMS of Ukraine
    5, Amosova Str., Kyiv, Ukraine, 03038
  3. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022
  4. Institute of Bioorganic Chemistry, NAS of Belarus
    5/2, Kuprevich Str., Minsk, Republic of Belarus, 220141

Abstract

The study of the effect of trimeric 2',5'-oligoadenytic acid (2',5'ApApA) and its epoxyderivative (2',5'-A2(RAA)) on both human immunodeficiency virus (HIV-1) reproduction and retro-viruses reverse transcriptase activity was conducted. 2',5'-oligo-adenylates were shown to suppress HIV-1 reproduction in case of their pre-incubation with the lymphoblastoid cells of MT-4 line. The possible mechanisms of antivirial action of 2' ,5'-oligoadenylates were under investigation, in particular, the interferonogenic effect of the substances was examined. 2',5'ApApA and 2',5'-A2(RAA) were shown to increase amounts of interferon in cells two and four-fold respectively compared to control. The inhibitory effect of 2',5'-oligoadenylates on activity of endogenous and exogenous retroviruses reverse transcriptase was demonstrated. The trimeric 2',5'-oligoadenylic acid and its epoxyderivative may be used against HIV infection.

References

[1] Muller WE, Schrodeer HC. Alteration of (2'-5')oligoadenylatee metabolism and ribonuclease L activity in H-9 cells by HIV. Int. Conf. AIDS., 1989 p. 667.
[2] Schroder HC, Wenger R, Kuchino Y, Muller WE. Modulation of nuclear matrix-associated 2',5'-oligoadenylate metabolism and ribonuclease L activity in H9 cells by human immunodeficiency virus. J Biol Chem. 1989;264(10):5669-73.
[3] Veda M, Higasa S, Suehiro A, Kakishita E. Evaluation of immuno-status in HIV disease using serum 2',5'-oligoadenylate synthetase activity. Int. Conf. AIDS., 1994; 10(1):158.
[4] Schroder HC, Kelve M, Muller WE. The 2-5A system and HIV infection. Prog Mol Subcell Biol. 1994;14:176-97.
[5] Schroder HC1, Suhadolnik RJ, Pfleiderer W, Charubala R, M?ller WE. (2'-5')Oligoadenylate and intracellular immunity against retrovirus infection. Int J Biochem. 1992;24(1):55-63.
[6] Mikhailopulo IA, Baran EA, Tkachuk LV. Synthesis and use in kidney transplantations in rabbits and monkeys of (2-5')oligoadenylate trimers modified at the 2'-terminus. 4th Int. symp. on Molecular aspects of chemotherapy, (23-25 June, 1993, Gdansk).-Gdansk 1993 p. 61.
[7] Viscidi R, Farzadegan H, Leister F, Francisco ML, Yolken R. Enzyme immunoassay for detection of human immunodeficiency virus antigens in cell cultures. J Clin Microbiol. 1988;26(3):453-8.
[8] Soloviev VD Pektemirov TA. Interferons in theory and practice meditsiny. M.: Medicine, 1981:85-90.
[9] Liu DK, Owens GF. Inhibition of viral reverse transcriptase by 2',5'-oligoadenylates. Biochem Biophys Res Commun. 1987;145(1):291-7.
[10] Kozlov AV, Tkachuk ZYu. Study of 2', 5'-oligoadenylates analogues stability to the action of phosphodiesterases Biopolym. Cell. 1994; 10(1):47-52
[11] Montefiori DC, Sobol RW Jr, Li SW, Reichenbach NL, Suhadolnik RJ, Charubala R, Pfleiderer W, Modliszewski A, Robinson WE Jr, Mitchell WM. Phosphorothioate and cordycepin analogues of 2',5'-oligoadenylate: inhibition of human immunodeficiency virus type 1 reverse transcriptase and infection in vitro. Proc Natl Acad Sci U S A. 1989;86(18):7191-4.
[12] Sobol RW, Fisher WL, Reichenbach NL, Kumar A, Beard WA, Wilson SH, Charubala R, Pfleiderer W, Suhadolnik RJ. HIV-1 reverse transcriptase: inhibition by 2',5'-oligoadenylates. Biochemistry. 1993;32(45):12112-8.