A LAT-ASSOCIATED FUNCTION REDUCES PRODUCTIVE-CYCLE GENE-EXPRESSION DURING ACUTE INFECTION OF MURINE SENSORY NEURONS WITH HERPES-SIMPLEX VIRUS TYPE-1

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