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 (HSV-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 environment in determining the outcome of infection. We describe a mouse model of HSV infection focused on motor neurons of the spinal cord, resulting 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 by 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 plaque assay for virus. Inflammation and cell destruction occurred in both models, but clinical features and histological destruction were greater in the group infected via the intramuscular route. In the sensory ganglia, a latent state from which virus could be reactivated by explanation, was established with LATS expression detectable in many neurons at 35 days post-infection (p.i.), but not in non-neuronal cells. Expression of latency associated transcript (LATS) was detected in motor neutrons in spinal cords at 35 days p.i. providing evidence for establishment of a LATS-positive latent state at this site, and continued to be detectable up to 6 months post-infection. In addition, LATS was detected in white matter at late times, suggesting a non-neuronal site of latency. In contrast to the behaviour in sensory ganglia, induced reactivation from spinal cords, by explanation and nerve section, was a very rare event. We have shown that a LATS-positive latent state can be established within motor neurons of the CNS, but that there are regional differences in the biology and outcome of infection between the CNS and peripheral nervous system. We propose that this may be a useful model to study reproducibly, the behaviour of HSV-1 in a CNS environment and, by comparison with sensory ganglion infection, to explore host factors which may underlie these regional differences. The relevance of this model for using HSV-1 as a therapeutic vector for motor neurons is also discussed.