Neuronal control of herpes simplex virus latency.

Herpes simplex virus (HSV) is a common neurotropic virus, and latent infection of sensory ganglion neurons readily occurs in humans and in experimentally infected animals. During HSV latency, infectious virus and viral antigen are not detected, and HSV transcription is limited to specific RNA termed latency-associated transcript (LAT). In the present study, the effect of altered nervous system function on HSV latent infection was investigated in dorsal root ganglia (drg) of experimentally infected mice. Latent infection of lumbar drg was established by footpad inoculation of HSV. During latency, sciatic neurectomy was performed in order to modify the in vivo function of latently infected neurons, and HSV LAT and HSV DNA in drg were investigated. Neurectomy has been used in many neurobiological studies to alter neuronal RNA and protein expression. After neurectomy there was a marked decrease in the number of LAT-positive neurons and in the amount of ganglion LAT. This was determined by in situ and RNA (Northern) blot hybridization. The neurectomy-related decrease of HSV LAT was apparent 9-10 days after neurectomy and was more marked after 21 days. The decrease was noted both in drg latently infected with standard thymidine kinase-positive (TK+) HSV and in ganglia infected with mutant TK- HSV. Since TK- HSV is largely reactivation defective, it is concluded that the neurectomy-induced decrease of LAT was probably not the result of in vivo HSV reactivation. It is acknowledged, however, that abortive reactivation by TK- HSV may occur, and decrease of latency may have resulted from neuronal or other host mechanisms subsequent to this. In order to investigate residual HSV latency, in addition to viral transcription, HSV DNA in drg was evaluated by polymerase chain reaction techniques. Decrease of HSV DNA was noted after neurectomy in drg latently infected with either TK+ or TK- HSV. It is suggested that the decrease in LAT expression detected was due to the change in neuronal transcription which is part of the neurectomy-induced axon reaction. Decreased HSV LAT may have led to decreased HSV DNA and latency. The decrease in the molecular markers of HSV latency following neurectomy emphasized the importance of neuronal control mechanisms in the pathogenesis of HSV latent infection.