Regulation of herpes simplex virus type 1 replication in Vero cells by Psychotria serpens: relationship to gene expression, DNA replication, and protein synthesis

Inhibitory effects of ethanolic extracts from seven Chinese herbs on herpes simplex virus type 1 (HSV-1) replication were investigated. From a bioassa y-guided fractionation procedure, PS-A-6 was isolated from Psychotria serpe ns (P. serpens), which suppressed HSV-1 multiplication in Vero cells withou t apparent cytotoxicity. Time-of-addition experiments suggested that the in hibitory action of PS-A-6 on HSV-1 replication was not through blocking of virus adsorption. In an attempt to further localize the point in the HSV-1 replication cycle where arrest occurred, a set of key regulatory events lea ding to viral multiplication was examined, including viral gene expression, DNA replication, and structural protein synthesis. The results indicated t hat gB mRNA and protein expression in Vero cells were impeded by PS-A-6. So uthern blot analysis showed that HSV-1 DNA replication in Vero cells was ar rested by PS-A-6. In addition, PS-A-6 decreased thymidine kinase (tk) and I CP27 mRNA expression in the cells. The mechanisms of antiviral action of PS -A-6 seem to be mediated, at least in part, through inhibition of early tra nscripts of HSV-1, such as tk and ICP27 mRNAs, arresting HSV-1 DNA synthesi s and gB gene expression in Vero cells. Plans are underway for the isolatio n of pure compounds from PS-A-6 and elucidation of their mechanism of actio n. (C) 2001 Elsevier Science B.V. All rights reserved.