Recurrent herpes simplex virus type 1 (HSV-1) ocular infections are the leading infectious cause of blindness in industrialized nations. Fewer than 10% of clinical cases are primary acute infections; the remaining 90% are recurrences of latent HSV-1. Although HSV-1 can reactivate spontaneously, stress and trauma (e.g., hypo- and hyperthermia, ultraviolet light irradiation, and ocular surgery) can also reactivate latent HSV-1. The latency-associated transcript (LAT) gene has been implicated as a component of the pathway that induces the conversion from latency to an acute infectious state. While the LAT gene is known to be the only gone that is abundantly transcribed during latency, it does not appear to code for any known protein. Furthermore, the LAT transcript that accumulates during latency is not the coding region, but is probably a stable 2.0 kb intron that is spliced out of the primary 8.5 kb LAT transcript. This proposal aims to dissect out the transcriptional control of the LAT promoter and its associated enhancer region from three distinct strains of HSV-1. These three strains of HSV-1 differ in their ability to undergo spontaneous and stress-induced reactivation. If the pathway by which the virus senses and responds to adrenergic stimuli can be established, it should prove to be a rich source of therapeutic targets. This is desirable since antiviral therapy merely delays the onset of blindness and viruses may become resistant to treatment. The specific aims that will address this issue are: 1) To assess the efficacy of the three LAT promoter regions in driving luciferase production in neuronal and fibroblast cell cultures, 2) To assess the effect of the three LAT enhancer regions on luciferase production in neuronal and fibroblast cell cultures, and 3) To assess the effect of different combinations of LAT promoters and enhancers on luciferase production in neuronal and fibroblast dell cultures.