Lack of effect of treatment with penciclovir or acyclovir on the establishment of latent HSV-1 in primary sensory neurons in culture

Recent studies suggest reductions in establishment of herpes simplex virus, type 1 (HSV-1) latency using the nucleoside analog penciclovir compared with acyclovir in the murine model. These observations raise the possibility that the new analogs may have novel activities that directly interfere with the establishment of the latent infection, suggesting a mechanism other than simply blocking the productive infection. To determine if penciclovir has a direct action on the establishment of latency, we compared the effects of penciclovir versus acyclovir in an in vitro model of HSV-1 latency in rat dorsal root ganglia neurons in culture. In neurons in culture, both penciclovir and acyclovir were highly effective in blocking the productive infection. However, neither penciclovir nor acyclovir blocked establishment of latency as demonstrated by similar percentages of neurons expressing the latency-associated transcript (LAT). Following removal of the respective nucleoside analog, latency was maintained until reactivation was induced by nerve growth factor deprivation. Similar virus titers were recovered after induction of reactivation of latent infections, which were established in the presence of either penciclovir or acyclovir. These results indicate that neither penciclovir nor acyclovir treatment directly prevents the establishment of latent HSV-1 infections in primary sensory neurons in culture.