The effects of topical application of phosphonoacetic acid on the colonization of mouse trigeminal ganglia by herpes simplex virus type 1 were examined. The results showed that the extent of colonization of ganglia by virus is related to the time elapsed between virus inoculation and application of this agent. In most cases, treatment started up to 12 h after inoculation prevented invasion of ganglia by virus HSV (4, 6, 7,13,15,17). Compounds such as arabinosyl adenine or arabinosyl adenine monophosphate are ineffective on comparably early application (5).There is no information, however, on the extent to which antiviral compounds can limit the amount of virus which invades the ganglia during the acute phase of infection. This information is important, since the amount of virus invading ganglia during the early phase of infection may determine the severity of the primary episode and the number of latently infected neurons and could also influence the frequency of subsequent recurrent episodes and the duration of HSV latency.In the present study, we determined the titer of infectious virus detectable in trigeminal ganglia of mice after a series of topical applications of PAA initiated at various intervals after virus inoculation. Furthermore, we monitored on a daily basis, during and after the end of the antiviral treatment, the evolution of virus titers in trigeminal ganglia and the inoculated skin area of HSV-infected mice. The results indicate that the interval between virus inoculation and initiation of antiviral treatments has an important influence on the amount of virus which accumulates in ganglia and determines, to a large extent, the outcome of the experimental HSV infection.MATERIALS AND METHODS Virus. HSV type 1 (HSV-1) strain S was used in all experiments. The maintenance of this strain, the preparation * Corresponding author. of stock virus, and the quantification of inocula have been described previously (3-7). This strain has the ability to invade the nervous system and to establish acute and latent infections in sensory ganglia.Inoculation of mice. Female hairless mice, strain HRS/J, obtained from Jackson Laboratories, Bar Harbor, Maine, were used in the experiments at the age of 6 to 8 weeks. They were inoculated percutaneously on a triangular area of the snout by rubbing a virus suspension containing 106 PFU/ml into the scarified skin. With this procedure, ca. 104 PFU were applied on the scarified skin of each mouse. Monitoring of infectious virus in sensory ganglia and skin specimens. At various intervals after inoculation, groups of mice were exsanguinated by heart puncture under pentobarbital sodium anesthesia. The day on which each group of mice was to be sacrificed had been randomly assigned after virus inoculation. Sensory ganglia were removed and homogenized immediately by sonication (Branson Sonifier Cell Disruptor 200). Skin specimens were removed from the inoculation area (ca. 0.25 cm2) and homogenized by sonication. The tissue suspension was clarified by centrifugation, and its viru...
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