Inhibition by interferon of herpes simplex virus thymidine kinase and DNA polymerase in infected and biochemically transformed cells

J Gen Virol. 1983 Sep;64 (Pt 9):1999-2006. doi: 10.1099/0022-1317-64-9-1999.

Abstract

The induction of thymidine kinase (TK) and DNA polymerase was inhibited by interferon (IFN) in mouse L-cells infected with herpes simplex virus type 1 (HSV-1). The inhibitory activity of IFN at this early stage of HSV-1 replication was followed by a reduced virus yield and was dependent on the multiplicity of infection. The expression of a cloned thymidine kinase (tk) gene of HSV-1, in biochemically transformed L-cells (LTK+), was not affected by IFN. These same LTK+ cells, however, developed an antiviral state since, upon HSV-1 infection, the induction of TK and DNA polymerase of the replicating virus was inhibited by IFN. Furthermore, IFN inhibited the transactivation of the HSV-1 tk gene in the biochemically transformed LTK+ cells, which followed infection by a virus mutant defective in the tk gene (HSV-1 TK-). This transactivation is dependent on expression of immediate-early HSV-1 alpha-genes. These results indicate that IFN inhibits HSV-1 replication at an early step prior to DNA synthesis. In addition, IFN displays a differential effect on the HSV-1 thymidine kinase gene, either when part of the replicating virus or when expressed as a cellular gene in biochemically transformed cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Viral / drug effects*
  • Clone Cells / microbiology
  • DNA-Directed DNA Polymerase / genetics
  • Enzyme Induction / drug effects
  • Genes, Viral / drug effects
  • Interferons / pharmacology*
  • L Cells / microbiology
  • Mice
  • Mutation
  • Nucleic Acid Synthesis Inhibitors*
  • Simplexvirus / drug effects*
  • Simplexvirus / enzymology
  • Simplexvirus / genetics
  • Thymidine Kinase / antagonists & inhibitors*
  • Thymidine Kinase / genetics
  • Virus Cultivation

Substances

  • Nucleic Acid Synthesis Inhibitors
  • Interferons
  • Thymidine Kinase
  • DNA-Directed DNA Polymerase