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Inhibition by Interferon of Herpes Simplex Virus Thymidine Kinase and DNA Polymerase in Infected and Biochemically Transformed Cells

Department of Virology, The Hebrew University — Hadassah Medical School, Jerusalem, Israel

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 -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.

Keywords: HSV-1, gene expression, IFN action, inhibition

Received 11 January 1983; accepted 9 May 1983.