Herpes simplex virus-1 (HSV-1) is a human trophic virus capable of establishing lifelong latent infections in the neurons of the peripheral nervous system of human hosts. HSV-1 infects the host via the mucosa and skin where it replicates in epithelial cells [ 1]. Following this initial infection, the virus then enters and infects the sensory nerves of the dorsal root ganglia (DRG) or trigeminal ganglia neurons innervating the site of infection. The virus is then transported to the neuronal cell body where the viral genome is deposited in the nucleus, thereby establishing a lifelong latent infection. Viral reactivation leads to virus replication in the neuronal cell body and virus transport along nerves to the nerve terminals for subsequent spread into the skin or mucosa, resulting in either recurrent disease or asymptomatic virus shedding [ 1].
The aim of our study is to define how HSV-1 exits sensory nerves to spread to the skin during recurrent herpes. We used primary DRG neurons grown in a compartmentalized neuronal culture system that physically and fluidically separates axons from their neuronal cell bodies into two compartments. This system allows HSV-1 infection of neuronal cell bodies in one compartment and the separate treatment of axons in the second compartment [ 2]. Confocal microscopy was used to visualize viral and cellular proteins along axons, whereas electron microscopy of axons sectioned in their growth plane was used to visualize viral particles along axons and axonal growth cones located at the axon terminals [ 3].
Using this compartmentalized neuronal culture system, we showed that an intact actin cytoskeleton is required for final release of HSV-1 from axons and that myosin V is as a key molecular motor involved in this process [ 4].