EFFECTS OF PENCICLOVIR AND FAMCICLOVIR IN A MURINE MODEL OF ENCEPHALITIS INDUCED BY INTRANASAL INOCULATION OF HERPES-SIMPLEX VIRUS TYPE-1

Mice inoculated intranasally with a potentially lethal dose of HSV-1 (strain SC16) were used to evaluate the efficacy of penciclovir (PCV) and its oral form, famciclovir (FCV) in the treatment of acute herpes encephalitis. In a comparative experiment, orally administered PCV was less effective than ganciclovir (GCV) in reducing mortality of infected mice, but was of similar effectiveness to acyclovir (ACV). Late deaths from ongoing infections were observed following cessation of treatment with both ACV and FCV. Delaying the onset of treatment by more than 1 day post infection markedly reduced the ability of orally administered ACV, PCV, and FCV to prevent death. Treatment from day 1 with FCV administered ad libitum in the drinking water resulted in rapid clearance of infectious virus from all parts of the brain, but latent virus was detected by Southern blot hybridization in the peripheral and central nervous system of survivors 1 month post infection. In untreated mice, infectious virus was also detected in the epithelium of the turbinate bones and in the lungs from 1 day after intranasal inoculation, and acute inflammatory changes were seen in the lungs. FCV was more effective in clearing virus from the lungs than from the turbinate bones in these mice. These data, concerning the importance of virus replication in the respiratory tract with regard to subsequent encephalitis, are considered to be a novel aspect of this study.