Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1977 Feb;11(2):299–306. doi: 10.1128/aac.11.2.299

Combined Antiviral Effects of Interferon, Adenine Arabinoside, Hypoxanthine Arabinoside, and Adenine Arabinoside-5′-Monophosphate in Human Fibroblast Cultures

Yvonne J Bryson 1,1, L H Kronenberg 1
PMCID: PMC351971  PMID: 848937

Abstract

Adenine arabinoside and human interferon are currently being evaluated in clinical trials against herpes- and poxvirus infections. Interferon production is also a normal antiviral response. It is therefore important to examine the combined actions of interferon and antiviral arabinosides for possible synergy or antagonism. We have examined the antiviral activities of human fibroblast interferon, adenine arabinoside, hypoxanthine arabinoside, and adenine arabinoside 5′-monophosphate individually, using plaque inhibition of vaccinia and herpes simplex type 2 viruses in human skin fibroblast cultures. By combining doses of interferon and arabinosides that, acting alone, give intermediate degrees of plaque inhibition, we were able to compare the combined antiviral activity with that calculated from the activity of each inhibitor alone, assuming that the activities are statistically independent. Our results show that the plaque-inhibitory activities of interferon and the arabinosides tested are statistically independent. The results also show that the arabinosides do not destabilize the antiviral state previously induced by interferon, and that interferon pretreatment does not interfere with subsequent arabinoside action in infected cells. We have also found that arabinosides do not affect the induction of interferon synthesis by either Newcastle disease virus or double-stranded ribonucleic acid, and are not themselves interferon inducers.

Full text

PDF
299

Selected References

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

  1. Armstrong J. A. Semi-micro, dye-binding assay for rabbit interferon. Appl Microbiol. 1971 Apr;21(4):723–725. doi: 10.1128/am.21.4.723-725.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bryson Y. J., Connor J. D. In vitro susceptibility of varicella zoster virus to adenine arabinoside and hypoxanthine arabinoside. Antimicrob Agents Chemother. 1976 Mar;9(3):540–543. doi: 10.1128/aac.9.3.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bryson Y., Connor J. D., Sweetman L., Carey S., Stuckey M. A., Buchanan R. Determination of plaque inhibitory activity of adenine arabinoside (9-beta-D-arabinofuranosyladenine) for herpesviruses using an adenosine deaminase inhibitor. Antimicrob Agents Chemother. 1974 Jul;6(1):98–101. doi: 10.1128/aac.6.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ch'ien L. T., Cannon N. J., Charamella L. J., Dismukes W. E., Whitley R. J., Buchanan R. A., Alford C. A., Jr Effect of adenine arabinoside on severe Herpesvirus hominis infections in man. J Infect Dis. 1973 Nov;128(5):658–663. doi: 10.1093/infdis/128.5.658. [DOI] [PubMed] [Google Scholar]
  5. Ch'ien L. T., Cannon N. J., Whitley R. J., Diethelm A. G., Dismukes W. E., Scott C. W., Buchanan R. A., Alford C. A., Jr Effect of adenine arabinoside on cytomegalovirus infections. J Infect Dis. 1974 Jul;130(1):32–39. doi: 10.1093/infdis/130.1.32. [DOI] [PubMed] [Google Scholar]
  6. Ch'ien L. T., Whitley R. J., Nahmias A. J., Lewin E. B., Linnemann C. C., Jr, Frenkel L. D., Bellanti J. A., Buchanan R. A., Alford D. A., Jr Antiviral chemotherapy and neonatal herpes simplex virus infecition: a pilot study--experience with adenine arabinoside (ARA-A). Pediatrics. 1975 May;55(5):678–685. [PubMed] [Google Scholar]
  7. Connor J. D., Sweetman L., Carey S., Stuckey M. A., Buchanan R. Effect of adenosine deaminase upon the antiviral activity in vitro of adenine arabinoside for vaccinia virus. Antimicrob Agents Chemother. 1974 Nov;6(5):630–636. doi: 10.1128/aac.6.5.630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. De Maeyer-Guignard J., Cachard A., De Maeyer E. Delayed-type hypersensitivity to sheep red blood cells: inhibition of sensitization by interferon. Science. 1975 Nov 7;190(4214):574–576. doi: 10.1126/science.1188355. [DOI] [PubMed] [Google Scholar]
  9. Duesberg P. H., Robinson W. S. Isolation of the nucleic acid of Newcastle disease virus (NDV). Proc Natl Acad Sci U S A. 1965 Sep;54(3):794–800. doi: 10.1073/pnas.54.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gisler R. H., Lindahl P., Gresser I. Effects of interferon on antibody synthesis in vitro. J Immunol. 1974 Aug;113(2):438–444. [PubMed] [Google Scholar]
  11. Johnson H. M., Smith B. G., Baron S. Inhibition of the primary in vitro antibody response by interferon preparations. J Immunol. 1975 Jan;114(1 Pt 2):403–409. [PubMed] [Google Scholar]
  12. Kronenberg L. H., Friedmann T. Relative quantitative assay of the biological activity of interferon messenger ribonucleic acid. J Gen Virol. 1975 May;27(2):225–238. doi: 10.1099/0022-1317-27-2-225. [DOI] [PubMed] [Google Scholar]
  13. Lerner A. M., Bailey E. J. Synergy of 9-beta-D-arabinofuranosyladenine and human interferon against Herpes simplex virus, type 1. J Infect Dis. 1974 Nov;130(5):549–552. doi: 10.1093/infdis/130.5.549. [DOI] [PubMed] [Google Scholar]
  14. Lindahl P., Leary P., Gresser I. Enhancement by interferon of the specific cytotoxicity of sensitized lymphocytes. Proc Natl Acad Sci U S A. 1972 Mar;69(3):721–725. doi: 10.1073/pnas.69.3.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nathenson G., Zakzewski B. Current status of passive immunity to diphtheria and tetanus in the newborn. J Infect Dis. 1976 Feb;133(2):199–201. doi: 10.1093/infdis/133.2.199. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES