Herpes simplex virus 1 (HSV-1) is widely spread among adults in the United States with a seroprevalence of about 60%. HSV-1 infects epithelial cells and then spreads to axonsinnervating those tissues causing potentially neuroinvasive reactivable episodes that may result in either mild lesions of the epithelia or fatal encephalitis in a partially understood process. We are interested in the HSV-1 clinical strain H129 because it is the only virus of any type known to egress exclusively in the anterograde direction. The retrograde spread from post-synaptic neuron to pre-synaptic neuron is impaired in this strain. There is no clear explanation for this unique phenotype and we are attempting to demonstrate the relationship between the phenotype of H129 strain and specific mutations in viral genes UL36 and UL1. Our hope is to establish a clear association between phenotype and genotype in the H129 strain. This research will improve the knowledge of both HSV-1 biology and host neural circuit organization that has been impossible to obtain in the past and may lead to the discovery of novel targets for antiviral compounds.