Effects of Sodium Valproate on the Replication of Herpes Simplex Virus Type 1: An in Vitro Study

Abstract

Background: Sodium valproate, an anticonvulsant drug, is reported to stimulate Human Immunodeficiency Virus type 1 and Human cytomegalovirus replication. Since epileptic patients undergoing sodium valproate therapy may suffer from various virus infections, the effect of this drug on replication of viruses especially those affecting neuronal tissues such as Herpes simplex virus type 1 is worthy of investigation. Methods: Viral replication was studied by quantal response method. Electron microscopy was also performed on cell monolayers treated with the drug and infected with the virus. Results: Significant reduction in viral infectivity was observed in cell cultures exposed to 0.5-2 mM of sodium valproate either one hr before or after infection. The corresponding electron microscopic examination revealed a very few intracytoplasmic enveloped virions and a marked reduction in the number of intracytoplasmic nucleocapsids in drug-treated virus infected cells compared with those of infected control. However, significant stimulation of virus replication was found upon treatment of cells with 1 mM (p<0.01) and 2 mM (p<0.001) of the drug 24 hours prior to infection. No remarkable change was seen in corresponding electron micrographs. Conclusion: Although the ultimate outcome of this study awaits in vivo assessments, possible stimulation of Herpes simplex virus type 1 replication by sodium valproate should be considered by clinicians prescribing this drug.Iran J Med Sci 2006; 31(1): 28-32. Keywords ● HSV-1 ● Sodium valproate ● inhibition ● electron microscopy