Effect of a thymidine kinase inhibitor (L-653,180) on antiviral treatment of experimental herpes simplex virus infection in mice.

Thymidine kinase (TK) inhibitors can block the activity of TK-dependent antiviral drugs in vitro. We have examined the ability of the TK inhibitor (+/-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl] methyl)guanine (L-653,180) to prevent the therapeutic effect of acyclovir (ACV) in experimental herpes simplex virus type 1 (HSV) skin infections of mice. The results showed that ACV given in the drinking water prevents, in a dose-dependent way, the evolution of the viral infection, and that L-653,180 can reverse some of the therapeutic effects of the antiviral drug. Among the parameters used to evaluate the effect of the TK inhibitor mortality was increased compared to ACV treatment alone, only in the presence of low doses of ACV, whereas the establishment of latent infections in sensory ganglia was significantly increased compared to ACV treatment alone, even when high doses of ACV were administered together with L-653,180.