EXPERIMENTAL HERPES-SIMPLEX VIRUS TYPE-1 (HSV-1) INFECTION OF THE SPINAL-CORD AND DORSAL-ROOT GANGLIA

Host factors determining the outcome of herpes simplex virus type 1 (H SV-1) infection within neurons are poorly understood. This paper aims to identify regional differences in the behaviour of HSV-1 within the nervous system as an approach to investigating the role of the host en vironment in determining the outcome of infection. We describe a mouse model of HSV infection focused on motor neurons of the spinal cord, r esulting from intramuscular injection (i.m.) and compare this with the behaviour of virus within sensory neurons following scarification of virus on to skin. Viral antigen was detectable immunohistochemically b y 2 days in both models and disappeared by 9-11 days, The time course of acute infection was reflected in the i.m. group by quantitative pla que assay for virus. Inflammation and cell destruction occurred in bot h models, but clinical features and histological destruction were grea ter in the group infected via the intramuscular route. In the sensory ganglia, a latent state from which virus could be reactivated by expla nation, was established with LATS expression detectable in many neuron s at 35 days post-infection (p.i.), but not in non-neuronal cells. Exp ression of latency associated transcript (LATS) was detected in motor neutrons in spinal cords at 35 days p.i. providing evidence for establ ishment of a LATS-positive latent state at this site, and continued to be detectable up to 6 months post-infection. In addition, LATS was de tected in white matter at late times, suggesting a non-neuronal site o f latency. In contrast to the behaviour in sensory ganglia, induced re activation from spinal cords, by explanation and nerve section, was a very rare event. We have shown that a LATS-positive latent state can b e established within motor neurons of the CNS, but that there are regi onal differences in the biology and outcome of infection between the C NS and peripheral nervous system. We propose that this may be a useful model to study reproducibly, the behaviour of HSV-1 in a CNS environm ent and, by comparison with sensory ganglion infection, to explore hos t factors which may underlie these regional differences. The relevance of this model for using HSV-1 as a therapeutic vector for motor neuro ns is also discussed.