The inhibition of herpes simplex virus multiplication by nucleosides

Abstract

Deoxyadenosine and uridine in millimolar concentrations inhibit reversibly the multiplication of herpes simplex virus in a human epidermoid carcinoma line of cells (H.Ep. No. 2) by blocking RNA synthesis. This emerges from the following: 1. (1) The nucleosides inhibit RNA synthesis as measured in pulse-labeling experiments. 2. (2) The nucleosides block the synthesis of thymidine kinase (ATP: thymidine 5′-phosphotransferase, EC 2.7.1.21), a virus-induced enzyme, when added to cell suspensions immediately after infection. The enzyme continues to be made if the cells are treated 4 h after infection, i.e., after the onset of synthesis of the enzyme. 3. (3) The nucleosides block the synthesis of viral DNA when added to cell suspensions immediately after infection; viral DNA synthesis is not appreciably affected if the nucleosides are added after 6 h, i.e., after the onset of viral DNA synthesis. 4. (4) The nucleosides block viral multiplication if added immediately after infection. Virus multiplication continues albeit the yield is reduced if the nucleosides are added at 6 h, i.e., after the onset of synthesis of viral DNA and viral capsid protein. 5. (5) The inhibition is reversed by withdrawing the nucleosides and not by addition of one or more of the ribose or deoxyribose nucleosides.