An in vivo model of varicella-zoster virus latent infection of dorsal root ganglia

We describe here the first in vivo model of varicella-zoster virus (VZV) latent infection in the adult rat peripheral nervous system. Infected Mewo cells were injected subcutaneously along the spine of healthy adult rats. No clinical sign of infection was observed even 9 months after inoculation. Humoral immune response to VZV was detected in all infected animals throughout the study (9 months). The presence of viral material in dissociated and cultured dorsal root ganglia (DRG) from inoculated animals was studied by immunoperoxidase and in situ hybridization. When DRGs from infected animals were plated in culture from 1 month and up to 9 months after inoculation, viral nucleic acids and proteins were detected in neurons. Furthermore, trypsinization and subcultivation of infected neurons in culture is needed to reactivate infectious virus at least in some of the neurons. This model provides a useful tool for studying 1) the molecular mechanisms leading to an in vivo latency, 2) the role of the immune system, in particular cellular immunity, on the establishment, maintenance, and reactivation of latency, 3) the neurotropism of mutant viruses, and 4) the effects of antiviral agents.