The effects of lithium and potassium on macromolecular synthesis in herpes simplex virus-infected cells

1 Department of Infection and 2 Department of Physiology, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TJ, U.K. All herpes simplex virus (HSV) infected cell-specific polypeptides (ICSPs) were synthesized in the presence of lithium at a concentration (60 m M ) inhibitory to the production of infectious virus. Yields of certain ICSPs were increased and others, in particular glycoprotein C, decreased. HSV DNA synthesis was completely inhibited; synthesis and in vitro activities of HSV DNA polymerase and thymidine kinase were decreased but to a degree insufficient to account for the complete inhibition of HSV DNA synthesis. HSV DNA synthesis was inhibited to an equivalent degree by either incubation with 60 m M -lithium or by potassium starvation; both procedures decreased intracellular potassium by an equivalent amount as adjudged by X-ray microanalysis. We conclude that lithium inhibits HSV DNA synthesis by displacement of potassium from a potassium-dependent biochemical reaction or by other physiological changes brought about by the loss of cellular potassium. The possibility that lithium also directly inhibits a virus replicative event cannot be excluded. Received 16 July 1992; accepted 5 April 1993.