A MOLECULAR AND CELLULAR-MODEL TO EXPLAIN THE DIFFERENCES IN REACTIVATION FROM LATENCY BY HERPES-SIMPLEX AND VARICELLA-ZOSTER VIRUSES

There are marked similarities in the biological properties of the huma n neurotropic herpesviruses herpes simplex virus type 1 (HSV-1) and va ricella-zoster virus (VZV), including their ability to establish lifel ong latent infections in human peripheral sensory ganglia (PSG). Despi te this, their patterns of reactivation are quite different: HSV-1 rea ctivations occur many times during a lifetime, they are localized to t he cutaneous distribution of a single sensory nerve, they are not asso ciated with sensory symptomatology and their frequency decreases with age. VZV recurrence on the other hand is usually a single event which tends to appear with advancing age, its cutaneous eruption involves an entire dermatome and is usually extremely painful. To help explain th ese differences, we have formulated a model based on current knowledge of the molecular and cellular basis of latent infection in the nervou s system. We suggest that the amount of latent viral DNA and RNA in th e latently infected tissue (higher with HSV-1), the cellular location of latent virus (neuronal in HSV-1, probably nonneuronal in VZV), the presence or absence of viral replication in the PSG during reactivatio n together with the host immune response, are all key determinants of the clinical expression of viral reactivation.