THE ACTIVITY OF THE PSEUDORABIES VIRUS LATENCY-ASSOCIATED TRANSCRIPT PROMOTER IS DEPENDENT ON ITS GENOMIC LOCATION IN HERPES-SIMPLEX VIRUS RECOMBINANTS AS WELL AS ON THE TYPE OF CELL INFECTED

As do many other alphaherpesviruses, pseudorabies virus (PRV) transcri bes a limited portion of its viral genome in latently infected neurons during latency. The sequence of the PRV latency-associated transcript (LAT) is bounded on its 5' end by a putative promoter region which co ntains sequence elements similar to those characterized for the herpes simplex virus (HSV) LAT promoter. Using the bacterial beta-galactosid ase gene as a reporter, we have assayed PRV LAT promoter activity in t he genomic environment in recombinant HSVs. The PRV LAT promoter-beta- galactosidase reporter gene was recombined into the terminal and inter nal long repeat regions (R(L) regions), replacing the normal HSV LAT p romoter, the cap site, and the first 60 bases of the primary transcrip t. When recombined into the R(L) region, appreciable reporter gene exp ression was observed following infection of two cell lines of neuronal origin; little or no activity was seen with these recombinants follow ing infection of rabbit skin or mouse embryo fibroblasts. No significa nt expression was seen when the promoter was recombined into the gC lo cus in the long unique region in any of the cell types utilized. Such results suggest that the PRV latency promoter contains neuronal cell-s pecific elements and that the HSV R(L) region provides an appropriate genomic environment for the manifestation of that specificity.