Review articleDefining nervous system susceptibility during acute and latent herpes simplex virus-1 infection

- In this review, we describe recent findings in an experimental animal model of herpes simplex virus encephalitis that manifests a persistent lytic infection in a unique and important area of the brain, the ependymal region.
- We describe our results in terms of what is already known experimentally and relate that to the human condition.
- Central nervous system region-specific susceptibility is reviewed from both animal models and human case reports.
- Evidence of HSV-1 spontaneous reactivation during the latent stage of infection is also reviewed.

Herpes simplex viruses are neurotropic human pathogens that infect and establish latency in peripheral sensory neurons of the host. Herpes Simplex Virus-1 (HSV-1) readily infects the facial mucosa that can result in the establishment of a latent infection in the sensory neurons of the trigeminal ganglia (TG). From latency, HSV-1 can reactivate and cause peripheral pathology following anterograde trafficking from sensory neurons. Under rare circumstances, HSV-1 can migrate into the central nervous system (CNS) and cause Herpes Simplex Encephalitis (HSE), a devastating disease of the CNS. It is unclear whether HSE is the result of viral reactivation within the TG, from direct primary infection of the olfactory mucosa, or from other infected CNS neurons. Areas of the brain that are susceptible to HSV-1 during acute infection are ill-defined. Furthermore, whether the CNS is a true reservoir of viral latency following clearance of virus during acute infection is unknown. In this context, this review will identify sites within the brain that are susceptible to acute infection and harbor latent virus. In addition, we will also address findings of HSV-1 lytic gene expression during latency and comment on the pathophysiological consequences HSV-1 infection may have on long-term neurologic performance in animal models and humans.