Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1987 May;61(5):1586–1592. doi: 10.1128/jvi.61.5.1586-1592.1987

Accumulation of 2',5'-oligoadenylates in encephalomyocarditis virus-infected mice.

W G Hearl, M I Johnston
PMCID: PMC254139  PMID: 2437319

Abstract

Levels of 2',5'-oligoadenylates (2-5A) in various tissues of murine encephalomyocarditis virus (EMCV)-infected mice were determined and compared with those found in pathogen-free mice and in mice treated with the interferon inducer poly(I).poly(C). In control, pathogen-free mice, liver, spleen, brain, and kidney tissues possessed levels of 2-5A below 1 pmol/g of tissue, demonstrating that 2-5A was not a major component of uninfected mouse tissue. All control tissues had low basal levels (0.3 to 2.0 pmol/h per g) of 2-5A synthetase, the enzyme responsible for 2-5A production. After mice were injected intravenously with the interferon inducer poly(I).poly(C), circulating interferon, 2-5A synthetase, and 2-5A were elevated with increasing doses of double-stranded RNA. The greatest response to poly(I).poly(C) occurred in the kidney, in which enzyme levels increased 5-fold and 2-5A levels increased 24-fold to 15 pmol/g. Mice that were infected with EMCV also possessed elevated levels of 2-5A and 2-5A synthetase in the four tissues examined, although the relative distribution differed from that observed with poly(I).poly(C), indicating that the interferon inducer affects the concentration and location of intracellular 2-5A. Brain, spleen, and kidney tissues from EMCV-infected mice contained seven- to eightfold more 2-5A than control tissues did. The nanomolar levels of 2-5A in the tissues of EMCV-infected mice provide evidence that 2-5A may play a role in the antiviral response in an intact animal. In both poly(I).poly(C)- and EMCV-treated mice, the levels of 2-5A recovered from the tissues were not directly proportional to the amount of 2-5A synthetase present. These results indicate that factors other than the level of 2-5A synthetase controlled the accumulation of 2-5A in tissues.

Full text

PDF
1586

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ball L. A. Induction, purification, and properties of 2'5' oligoadenylate synthetase. Ann N Y Acad Sci. 1980;350:486–496. doi: 10.1111/j.1749-6632.1980.tb20651.x. [DOI] [PubMed] [Google Scholar]
  2. Ball L. A., White C. N. Oligonucleotide inhibitor of protein synthesis made in extracts of interferon-treated chick embryo cells: comparison with the mouse low molecular weight inhibitor. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1167–1171. doi: 10.1073/pnas.75.3.1167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown R. E., Kerr I. M. (p)pp(A2'p)nA is rare in normal mouse tissues while (A2'p)nA but not (p)pp(A2'p)nA appears to be present in E. coli. Prog Clin Biol Res. 1985;202:3–10. [PubMed] [Google Scholar]
  4. Dougherty J. P., Samanta H., Farrell P. J., Lengyel P. Interferon, double-stranded RNA, and RNA degradation. Isolation of homogeneous pppA(2'p5'A)n-1 synthetase from Ehrlich ascites tumor cells. J Biol Chem. 1980 May 10;255(9):3813–3816. [PubMed] [Google Scholar]
  5. Dougherty J. P., Samanta H., Farrell P. J., Lengyel P. Interferon, double-stranded RNA, and RNA degradation. Isolation of homogeneous pppA(2'p5'A)n-1 synthetase from Ehrlich ascites tumor cells. J Biol Chem. 1980 May 10;255(9):3813–3816. [PubMed] [Google Scholar]
  6. Floyd-Smith G., Slattery E., Lengyel P. Interferon action: RNA cleavage pattern of a (2'-5')oligoadenylate--dependent endonuclease. Science. 1981 May 29;212(4498):1030–1032. doi: 10.1126/science.6165080. [DOI] [PubMed] [Google Scholar]
  7. Galaktidou G., Kortsaris A., Koliais S. I. Induction of 2',5' oligo(A) synthetase in tumor-bearing mice with encephalomyocarditis (EMC) virus or poly(I)poly(C). FEBS Lett. 1983 Nov 28;164(1):161–165. doi: 10.1016/0014-5793(83)80041-6. [DOI] [PubMed] [Google Scholar]
  8. Hersh C. L., Brown R. E., Roberts W. K., Swyryd E. A., Kerr I. M., Stark G. R. Simian virus 40-infected, interferon-treated cells contain 2',5'-oligoadenylates which do not activate cleavage of RNA. J Biol Chem. 1984 Feb 10;259(3):1731–1737. [PubMed] [Google Scholar]
  9. Hovanessian A. G., Youn J. K., Buffet-Janvresse C., Riviere Y., Michelson M., Lacour J., Lacour F. Enhancement of natural killer cell activity and 2-5A synthetase in operable breast cancer patients treated with polyadenylic; polyuridylic acid. Cancer. 1985 Jan 15;55(2):357–362. doi: 10.1002/1097-0142(19850115)55:2<357::aid-cncr2820550210>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  10. Imai J., Lesiak K., Torrence P. F. Respective role of each of the purine N-6 amino groups of 5'-O-triphosphoryladenylyl(2'----5')adenylyl(2----5')adenosine in binding to and activation of RNase L. J Biol Chem. 1985 Feb 10;260(3):1390–1393. [PubMed] [Google Scholar]
  11. Johnston M. I., Imai J., Lesiak K., Jacobsen H., Sawai H., Torrence P. F. Antibody-nucleic acid interactions. Monoclonal antibodies define different antigenic domains in 2',5'-oligoadenylates. Biochemistry. 1985 Aug 13;24(17):4710–4718. doi: 10.1021/bi00338a033. [DOI] [PubMed] [Google Scholar]
  12. Kerr I. M., Brown R. E. pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci U S A. 1978 Jan;75(1):256–260. doi: 10.1073/pnas.75.1.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimchi A., Shulman L., Schmidt A., Chernajovsky Y., Fradin A., Revel M. Kinetics of the induction of three translation-regulatory enzymes by interferon. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3208–3212. doi: 10.1073/pnas.76.7.3208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knight M., Cayley P. J., Silverman R. H., Wreschner D. H., Gilbert C. S., Brown R. E., Kerr I. M. Radioimmune, radiobinding and HPLC analysis of 2-5A and related oligonucleotides from intact cells. Nature. 1980 Nov 13;288(5787):189–192. doi: 10.1038/288189a0. [DOI] [PubMed] [Google Scholar]
  15. Krause D., Silverman R. H., Jacobsen H., Leisy S. A., Dieffenbach C. W., Friedman R. M. Regulation of ppp(A2'p)nA-dependent RNase levels during interferon treatment and cell differentiation. Eur J Biochem. 1985 Feb 1;146(3):611–618. doi: 10.1111/j.1432-1033.1985.tb08695.x. [DOI] [PubMed] [Google Scholar]
  16. Krishnan I., Baglioni C. Elevated levels of (2'-5')oligoadenylic acid polymerase activity in growth-arrested human lymphoblastoid Namalva cells. Mol Cell Biol. 1981 Oct;1(10):932–938. doi: 10.1128/mcb.1.10.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krishnan I., Baglioni C. Increased levels of (2'-5')oligo(A) polymerase activity in human lymphoblastoid cells treated with glucocorticoids. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6506–6510. doi: 10.1073/pnas.77.11.6506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Laurence L., Marti J., Roux D., Cailla H. Immunological evidence for the in vivo occurrence of (2'-5')adenylyladenosine oligonucleotides in eukaryotes and prokaryotes. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2322–2326. doi: 10.1073/pnas.81.8.2322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lodemann E., Kornhuber B., Gerein V., von Il'berg C. (2'-5')oligo(A) synthetase as a monitor of interferon action in juvenile laryngeal papillomatosis. J Interferon Res. 1984 Spring;4(2):283–290. doi: 10.1089/jir.1984.4.283. [DOI] [PubMed] [Google Scholar]
  20. Reid T. R., Hersh C. L., Kerr I. M., Stark G. R. Analysis of 2',5'-oligoadenylates in cells and tissues. Anal Biochem. 1984 Jan;136(1):136–141. doi: 10.1016/0003-2697(84)90315-4. [DOI] [PubMed] [Google Scholar]
  21. Samanta H., Dougherty J. P., Lengyel P. Synthesis of (2'-5')(A)n from ATP. Characteristics of the reaction catalyzed by (2'-5')(A)n synthetase purified from mouse Ehrlich ascites tumor cells treated with interferon. J Biol Chem. 1980 Oct 25;255(20):9807–9813. [PubMed] [Google Scholar]
  22. Sawai H., Ishibashi K., Itoh M., Watanabe S. 2',5'-Oligoadenylate and 2',5'-oligoadenylate phosphodiesterase in human plasma. Biochem Biophys Res Commun. 1984 Dec 28;125(3):1061–1066. doi: 10.1016/0006-291x(84)91391-3. [DOI] [PubMed] [Google Scholar]
  23. Schmidt A., Chernajovsky Y., Shulman L., Federman P., Berissi H., Revel M. An interferon-induced phosphodiesterase degrading (2'-5') oligoisoadenylate and the C-C-A terminus of tRNA. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4788–4792. doi: 10.1073/pnas.76.10.4788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shimizu N., Sokawa Y. 2',5'-Oligoadenylate synthetase activity in lymphocytes from normal mouse. J Biol Chem. 1979 Dec 10;254(23):12034–12037. [PubMed] [Google Scholar]
  25. Silverman R. H., Cayley P. J., Knight M., Gilbert C. S., Kerr I. M. Control of the ppp(a2'p)nA system in HeLa cells. Effects of interferon and virus infection. Eur J Biochem. 1982 May;124(1):131–138. doi: 10.1111/j.1432-1033.1982.tb05915.x. [DOI] [PubMed] [Google Scholar]
  26. Smekens-Etienne M., Goldstein J., Ooms H. A., Dumont J. E. Variation of (2'-5')oligo(adenylate) synthetase activity during rat-liver regeneration. Eur J Biochem. 1983 Feb 1;130(2):269–273. doi: 10.1111/j.1432-1033.1983.tb07146.x. [DOI] [PubMed] [Google Scholar]
  27. Stark G. R., Dower W. J., Schimke R. T., Brown R. E., Kerr I. M. 2-5A synthetase: assay, distribution and variation with growth or hormone status. Nature. 1979 Mar 29;278(5703):471–473. doi: 10.1038/278471a0. [DOI] [PubMed] [Google Scholar]
  28. Torrence P. F., Friedman R. M. Are double-stranded RNA-directed inhibition of protein synthesis in interferon-treated cells and interferon induction related phenomena? J Biol Chem. 1979 Feb 25;254(4):1259–1267. [PubMed] [Google Scholar]
  29. Torrence P. F., Imai J., Johnston M. I. 5'-O-Monophosphoryladenylyl(2' goes to 5')adenylyl(2' goes to 5')adenosine is an antagonist of the action of 5'-O-triphosphoryladenylyl-(2' goes to 5')adenylyl(2' goes to 5')adenosine and double-stranded RNA. Proc Natl Acad Sci U S A. 1981 Oct;78(10):5993–5997. doi: 10.1073/pnas.78.10.5993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Torrence P. F., Imai J., Johnston M. I. Assay of 2',5'-oligoadenylate phosphodiesterase activity in mouse L-cell extracts. Anal Biochem. 1983 Feb 15;129(1):103–110. doi: 10.1016/0003-2697(83)90058-1. [DOI] [PubMed] [Google Scholar]
  31. Verhaegen-Lewalle M., Content J. 2'-Phosphodiesterase activity in human cell lines treated or untreated with human interferon. Eur J Biochem. 1982 Sep 1;126(3):639–643. doi: 10.1111/j.1432-1033.1982.tb06828.x. [DOI] [PubMed] [Google Scholar]
  32. Vogel S. N., English K. E., O'Brien A. D. Silica enhancement of murine endotoxin sensitivity. Infect Immun. 1982 Nov;38(2):681–685. doi: 10.1128/iai.38.2.681-685.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wells J. A., Swyryd E. A., Stark G. R. An improved method for purifying 2',5'-oligoadenylate synthetases. J Biol Chem. 1984 Jan 25;259(2):1363–1370. [PubMed] [Google Scholar]
  34. Williams B. R., Golgher R. R., Brown R. E., Gilbert C. S., Kerr I. M. Natural occurrence of 2-5A in interferon-treated EMC virus-infected L cells. Nature. 1979 Dec 6;282(5739):582–586. doi: 10.1038/282582a0. [DOI] [PubMed] [Google Scholar]
  35. Williams G. J., De Benedetti A., Baglioni C. Inhibition of 2',5'-oligo(A)-dependent endoribonuclease by 2',5'-oligo(A) degradation products. Virology. 1986 Jun;151(2):233–242. doi: 10.1016/0042-6822(86)90045-0. [DOI] [PubMed] [Google Scholar]
  36. Wreschner D. H., McCauley J. W., Skehel J. J., Kerr I. M. Interferon action--sequence specificity of the ppp(A2'p)nA-dependent ribonuclease. Nature. 1981 Jan 29;289(5796):414–417. doi: 10.1038/289414a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES