THE MEMORY EFFECT OF HETEROPOLYOXOTUNGSTATE (PM-19) PRETREATMENT ON INFECTION BY HERPES SIMPLEX VIRUS AT THE PENETRATION STAGE

Abstract The keggin-type heteropolyoxotungstate K 7 [PTi 2 W 10 O 40 ]·6H 2 O (PM-19) is a potent polyoxometalate (PM) inhibitor of the replication of herpes simplex virus (HSV). Pretreatment of Vero cells with PM-19 prior to HSV-2 infection enhanced the antiviral potency of PM-19 almost 10-fold compared with treatment of the cells only after infection. The pretreatment effect of PM-19 is called ‘the memory effect’. The memory effect was reflected by inhibition of plaque formation and decrease of intracellular virus DNA quantity, and was strongest when PM-19 was present during the penetration stage of HSV-2 infection. The effect was maintained under conditions of fusion induced by polyethyleneglycol treatment. This suggests that PM-19 does not act at the fusion stage of infection. Using the infectious center assay method, it was clarified that a second round of infection was inhibited by about 30% in the presence of PM-19 at the penetration stage compared with the virus control in nontreated cells. The inhibition was enhanced to about 60% by PM-19 pretreatment prior to infection. This suggests that PM-19 pretreatment of the cells protects them against HSV-2 infection.