The Enquist Lab focuses on mechanisms of herpesvirus pathogenesis. Most alphaherpesviruses e.g., herpes simplex virus HSV; varicella-zoster virus, VZV; and pseudorabies virus, PRV) invade the peripheral nervous system (PNS) in their natural hosts. This life style is remarkable because of all the neurotropic viruses that also enter the PNS (e.g., rabies), only the alphaherpesviruses routinely STOP in the PNS of their natural hosts and establish a reactivatable, latent infection. Normally, this PNS infection is relatively benign, promoting survival of both virus and host. However, aberrations in this pathway give rise to the set of common diseases caused by these viruses. For example, invasion of the CNS is a rare, but an exceedingly serious possibility. The directional spread of a herpes infection from epithelial surfaces to PNS neurons where latency is established, and then, upon reactivation, spread back to epithelial surfaces constitutes the virus survival strategy. Research in my laboratory is directed toward answering several basic questions: What are the virus- and cell-encoded mechanisms that direct virus particles into and back out of the PNS? Why does the virus only occasionally enter the CNS in its natural host? What are the molecular roadblocks that make CNS infection rare in the natural host and frequent in the non-natural host? What are the viral gene products that promote efficient infection and how do they work? How do the PNS and CNS respond to viral infection? These basic questions continue to lead us into exciting and sometimes unexpected areas.