Nervous system inflammatory lesions and viral nucleic acids in rabbits with herpes simplex virus encephalitis-induced rotational behaviour.
Rabbits with herpes simplex virus (HSV) encephalitis induced by corneal virus challenge exhibit rotational behaviour linked with altered brain dopamine functions. The neuropathology and the distribution of the HSV-specific nucleic acids were studied, using probes for the viral trans-inducing factor alpha TIF and for the latency-associated transcript LAT-1 RNA to detect productive and latent infections, respectively. The rotational behaviour began 4 days after inoculation, and at that time the inflammatory process was observed only in the brain stem and the productive infection, revealed by in situ hybridisation, was seen in the trigeminal entry and nuclei. No HSV-specific nucleic acids or neural destruction were observed in the regions of the serotoninergic raphe or dopaminergic substantia nigra. At 8 days after inoculation, when the rotational behaviour was beginning to attenuate, the inflammatory lesions spread into the hemispheres, involving particularly the ventral parts of the limbic system including the olfactory system. In no cases were HSV-specific nucleic acids detected in the olfactory system. The inflammation in the limbic system was also detectable in animals without inflammatory lesions in the olfactory bulbs or tracts, suggesting that the infection had spread from the brain stem. The present study shows that in this model the altered neurotransmitter functions observed previously, appearing as rotational behaviour, occur without productive infection or necrosis, suggesting specific interaction of HSV with monoaminergic neurons. Additionally, the results suggest that HSV could reach the limbic system via ascending serotoninergic projections from the raphe neurons.