Characterization of the initiator and downstream promoter elements of herpes simplex virus 1 late genes.

Previously identified cis-acting regulatory elements of herpes simplex virus (HSV) 1 late promoters include a TATA element upstream from the start of transcription, an initiator-like element at the start of transcription, and sequences downstream from the start of transcription. To determine whether these elements are functionally equivalent to similar elements from other eukaryotic genes, model late promoters were constructed using well-characterized regulatory elements from non-HSV genes. These modular promoters were then inserted into the viral genome upstream from a lacZ marker gene. Results showed that a eukaryotic initiator element, along with a TATA element, can function as a late HSV promoter. Several initiator sequences from both viral and nonviral genes were functionally similar to the initiator-like element in HSV-1 late promoters; however, a random sequence of the same size and a similarly located sequence from the HSV-1 early thymidine kinase promoter could not substitute for the initiator element. These results indicate that eukaryotic initiator elements are functionally equivalent to HSV-1 late promoter initiator elements. In addition, the downstream element of the late glycoprotein C promoter was further analyzed by construction of a series of small deletions and insertions. The presence of the downstream glycoprotein C region in a promoter consisting of a strong TATA and initiator element increased mRNA expression by a modest amount; this effect appeared to be sequence specific and dependent on its exact alignment with the upstream elements of the promoter.