HERPES-SIMPLEX VIRUS LATENCY AFTER DIRECT GANGLION VIRUS INOCULATION

Herpes simplex virus (HSV) latent infection of ganglion neurons follow s axoplasmic transport of HSV, probably in the form of nucleocapsid fr om peripheral sites of infection (e.g, footpad). This raises the possi bility that latency is dependent on this particular means of presentin g HSV to ganglion neurons. To investigate this, we directly infected g anglia of mice with HSV and evaluated latency. Initially, ganglia were surgically exposed in intact mice, infected with HSV and after 4 week s evaluated for HSV latency-associated transcript (LAT) expression. LA T expression suggested latency. To more fully evaluate latency after d irect ganglion inoculation, a transplant model was developed. In this model, ganglia were removed from mice, inoculated with HSV, transplant ed into syngeneic recipients and evaluated for latency after several w eeks. Latency was evident in transplanted ganglia by (1) the presence of LAT in neurons; (2) the lack of HSV ICP4 RNA or viral antigen, and (3) the isolation of HSV from explants of transplants but not from dir ect homogenates. The transplant model was then used to evaluate the ef fect of inhibition of HSV replication on latency. Antivirals which inh ibited HSV replication markedly decreased the number of LAT-positive n eurons in transplants, suggesting a role for HSV replication mechanism s and latency. It is thought that direct ganglion inoculation and gang lion transplant methods will permit unique investigations of mechanism s of latency.