Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Apr;38(4):853–856. doi: 10.1128/aac.38.4.853

Regulation of herpes simplex virus thymidine kinase in cells treated with a synergistic antiviral combination of alpha interferon and acyclovir.

J L Taylor 1, P Tom 1, J Guy 1, R M Selvarajan 1, W J O'Brien 1
PMCID: PMC284554  PMID: 8031058

Abstract

Alpha interferon (IFN-alpha) and acyclovir (ACV) are synergistic in their anti-herpes simplex virus activities. IFN-alpha treatment reduced the herpes simplex virus thymidine kinase (TK) activity present in cells 6 h postinfection, while steady-state levels of TK mRNA remained at or above the amount in infected, untreated cells. The inhibition of TK production by IFN-alpha treatment appeared to be transient and translational, not transcriptional.

Full text

PDF
853

Images in this article

854Image
on p.854

Selected References

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

  1. Altinkilic B., Brandner G. Interferon inhibits herpes simplex virus-specific translation: a reinvestigation. J Gen Virol. 1988 Dec;69(Pt 12):3107–3112. doi: 10.1099/0022-1317-69-12-3107. [DOI] [PubMed] [Google Scholar]
  2. De Stasio P. R., Taylor M. W. Trans-activation of herpes simplex virus type 1 immediate early genes is specifically inhibited by human recombinant interferons. Biochem Biophys Res Commun. 1989 Mar 15;159(2):439–444. doi: 10.1016/0006-291x(89)90011-9. [DOI] [PubMed] [Google Scholar]
  3. Furman P. A., St Clair M. H., Spector T. Acyclovir triphosphate is a suicide inactivator of the herpes simplex virus DNA polymerase. J Biol Chem. 1984 Aug 10;259(15):9575–9579. [PubMed] [Google Scholar]
  4. Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem. 1978 Dec 25;253(24):8721–8727. [PubMed] [Google Scholar]
  5. Gloger I., Panet A. Synthesis of herpes simplex virus proteins in interferon-treated human cells. J Gen Virol. 1984 Jun;65(Pt 6):1107–1111. doi: 10.1099/0022-1317-65-6-1107. [DOI] [PubMed] [Google Scholar]
  6. Gompels U., Minson A. The properties and sequence of glycoprotein H of herpes simplex virus type 1. Virology. 1986 Sep;153(2):230–247. doi: 10.1016/0042-6822(86)90026-7. [DOI] [PubMed] [Google Scholar]
  7. Harris-Hamilton E., Bachenheimer S. L. Accumulation of herpes simplex virus type 1 RNAs of different kinetic classes in the cytoplasm of infected cells. J Virol. 1985 Jan;53(1):144–151. doi: 10.1128/jvi.53.1.144-151.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Henley D. C., Weir J. P. The relative stability of selected herpes simplex virus type 1 mRNAs. Virus Res. 1991 Jul;20(2):121–132. doi: 10.1016/0168-1702(91)90104-4. [DOI] [PubMed] [Google Scholar]
  9. McKnight S. L. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Res. 1980 Dec 20;8(24):5949–5964. doi: 10.1093/nar/8.24.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mittnacht S., Straub P., Kirchner H., Jacobsen H. Interferon treatment inhibits onset of herpes simplex virus immediate-early transcription. Virology. 1988 May;164(1):201–210. doi: 10.1016/0042-6822(88)90637-x. [DOI] [PubMed] [Google Scholar]
  11. Muñoz A., Carrasco L. Formation of non-infective herpesvirus particles in cultured cells treated with human interferon. J Gen Virol. 1984 Jun;65(Pt 6):1069–1078. doi: 10.1099/0022-1317-65-6-1069. [DOI] [PubMed] [Google Scholar]
  12. O'Brien W. J., Coe E. C., Taylor J. L. Nucleoside metabolism in herpes simplex virus-infected cells following treatment with interferon and acyclovir, a possible mechanism of synergistic antiviral activity. Antimicrob Agents Chemother. 1990 Jun;34(6):1178–1182. doi: 10.1128/aac.34.6.1178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Oberman F., Panet A. Characterization of the early steps of herpes simplex virus replication in interferon-treated human cells. J Interferon Res. 1989 Oct;9(5):563–571. doi: 10.1089/jir.1989.9.563. [DOI] [PubMed] [Google Scholar]
  14. Popik W., Pitha P. M. Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9573–9577. doi: 10.1073/pnas.88.21.9573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Read G. S., Sharp J. A., Summers W. C. In vitro and in vivo transcription initiation sites on the TK-encoding BamHI Q fragment of HSV-1 DNA. Virology. 1984 Oct 30;138(2):368–372. doi: 10.1016/0042-6822(84)90363-5. [DOI] [PubMed] [Google Scholar]
  16. Reardon J. E., Spector T. Herpes simplex virus type 1 DNA polymerase. Mechanism of inhibition by acyclovir triphosphate. J Biol Chem. 1989 May 5;264(13):7405–7411. [PubMed] [Google Scholar]
  17. Samuel C. E. Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities. Virology. 1991 Jul;183(1):1–11. doi: 10.1016/0042-6822(91)90112-o. [DOI] [PubMed] [Google Scholar]
  18. Schnipper L. E., Crumpacker C. S. Resistance of herpes simplex virus to acycloguanosine: role of viral thymidine kinase and DNA polymerase loci. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2270–2273. doi: 10.1073/pnas.77.4.2270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sharp J. A., Wagner M. J., Summers W. C. Transcription of herpes simplex virus genes in vivo: overlap of a late promoter with the 3' end of the early thymidine kinase gene. J Virol. 1983 Jan;45(1):10–17. doi: 10.1128/jvi.45.1.10-17.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Taylor J. L., Casey M. S., O'Brien W. J. Synergistic antiherpes virus activity of acyclovir and interferon in human corneal stromal cells. Invest Ophthalmol Vis Sci. 1989 Mar;30(3):365–370. [PubMed] [Google Scholar]
  21. Taylor J. L., Punda-Polic V., O'Brien W. J. Combined anti-herpes virus activity of nucleoside analogs and interferon. Curr Eye Res. 1991;10 (Suppl):205–211. doi: 10.3109/02713689109020381. [DOI] [PubMed] [Google Scholar]
  22. Thiele K., Kirchner H. Effects of different interferons on the replication of herpes simplex virus in human T lymphocytes. J Interferon Res. 1988 Aug;8(4):507–515. doi: 10.1089/jir.1988.8.507. [DOI] [PubMed] [Google Scholar]
  23. Tsang S. S., Yin X., Guzzo-Arkuran C., Jones V. S., Davison A. J. Loss of resolution in gel electrophoresis of RNA: a problem associated with the presence of formaldehyde gradients. Biotechniques. 1993 Mar;14(3):380–381. [PubMed] [Google Scholar]
  24. Wagner M. J., Sharp J. A., Summers W. C. Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1441–1445. doi: 10.1073/pnas.78.3.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES