Rodent models of varicella-zoster virus neurotropism.

Inoculation of rodents with varicella-zoster virus (VZV) results in a latent infection in dorsal root ganglia with expression of at least five of the six VZV transcripts and one of the viral proteins that are reported to be expressed during latency in human ganglia. Rats develop allodynia and hyperalgesia in the limb distal to the site of injection and the resulting exaggerated withdrawal response to stimuli is reduced by treatment with gabapentin and amitryptyline, but not by antiviral therapy. Inoculation of rats with VZV mutants show that most viral genes are dispensable for latency, but that some genes (e.g., ORF4, 29, and ORF63) that are expressed during latency are important for the establishment of latency in rodents, but not for infection of rodent ganglia. The rodent model for VZV latency allows one to study ganglia removed immediately after death, avoiding the possibility of reactivation, and helps to identify VZV genes required for latency.