Can herpes simplex virus latency be prevented using conventional nucleoside analogue chemotherapy?

This review summarizes work that has been published recently in several papers reporting the effects of famciclovir and valaciclovir therapy on the establishment of herpes simplex virus (HSV) latency in a murine cutaneous infection model. For both HSV-1 and HSV-2 infections, therapy with famciclovir or valaciclovir from 1 or 2 days after virus inoculation reduced the ability to reactivate infectious virus from explanted ganglia when this was attempted several weeks after the primary infection. For famciclovir, the reduced ability to reactivate virus was also apparent in mice in which the onset of therapy was delayed for up to 3-5 days after virus inoculation. When more sensitive methods were employed to detect latency, all mice were found to be positive for latent infections in the ganglia, including those from mice receiving early therapy. However, for mice that had received oral famciclovir treatment the relative number of latently infected ganglion cells, as determined by infectious centres, appeared to be greatly reduced; this is thought to explain the failure to reactivate virus by means of the explant method. These results show a marked difference in activity between famciclovir and valaciclovir in this model and suggest that prompt therapy of first episode herpes by means of famciclovir may be able to reduce the establishment of latency in humans, where the establishment of latent infections in ganglionic neurons is thought to be a slower process than that observed in mice.