Herpes simplex virus (HSV) persists in the human population by establishing long-term latent infections followed by periodic reactivation and transmission. Latent infection of sensory neurons is characterized by repression of vital productive-cycle gene expression, with abundant transcription limited to a single locus that encodes the latency-associated transcripts (LATs). We have observed that LAT- deletion mutant viruses express viral productive-cycle genes in greater numbers of murine trigeminal ganglion neurons than LAT+ HSV type 1 at early times during acute infection but show reduced reactivation from latent infection. Thus, a vital function associated with the LAT region exerts an effect at an early stage of neuronal infection to reduce productive-cycle vital gene expression. These results provide the first evidence that the virus plays an active role in down- regulating productive infection during acute infection of sensory neurons. The effect of down-regulation of productive-cycle gene expression during acute infection may contribute to vital evasion from the host immune responses and to reduced cytopathic effects, thereby facilitating neuronal survival and the establishment of latency.