Herpes simplex virus evolved to use the human defense mechanisms to establish a lifelong infection in neurons--a review and hypothesis.

The review of recent studies using DNA microarrays shed new light on herpes simplex virus (HSV) replicative cycle, the response of immature dendritic cells (DCs) to pathogens and the response of neurons in trigeminal ganglia to virus reactivation. These studies provided a better understanding of the molecular biology of HSV during infection, latency and reactivation. The research on the sensory trigeminal neurons and the neuronal axons (type C fibers) that transverse the skin basal membrane, enter the skin epidermis and interact with the cell membrane of the skin resident immature DCs provided an insight on the connection between the nervous system and the host immune system. Based on these studies a hypothesis is presented suggesting that HSV evolved to use the human host defense systems (pain signals, the immune system cells and sensory neurons) to ensure its entry from the skin epithelium into the sensory neurons. Reactivated HSV in the neurons utilizes the same host defense systems to return to the skin epithelium.