The effects of lithium and potassium on macromolecular synthesis in herpes simplex virus-infected cells.
All herpes simplex virus (HSV) infected cell-specific polypeptides (ICSPs) were synthesized in the presence of lithium at a concentration (60 mM) 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 mM-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.
Department of Infection Medical School, University of Birmingham, Edgbaston, U.K.
C E
CE
Hartley
A
A
Buchan
S
S
Randall
G R
GR
Skinner
M
M
Osborne
L M
LM
Tomkins
D000818:Animals; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects* / Q000378:metabolism; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000187:drug effects; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D010455:Peptides; D008094:Lithium; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D011188:Potassium