The Initiator Element in a Herpes Simplex Virus Type 1 Late-Gene Promoter Enhances Activation by ICP4, Resulting in Abundant Late-Gene Expression

Abstract

The start site regions of late genes of herpes simplex virus type 1 are similar to the eukaryotic initiator sequence (Inr), have been shown to affect the levels of expression, and may also play a role in transcription activation by the viral activator ICP4. A series of linker-scanning mutations spanning the start site of transcription and several downstream mutations in the true late gC promoter were analyzed in reconstituted in vitro transcription reactions with and without ICP4, as well as in the context of the viral genome during infection. The nucleotide contacts previously found to be important for Inr function were also found to be important for optimal induction by ICP4. While the Inr had a substantial effect on the accumulation of gC RNA during infection, no other sequence downstream of the TATA box to +124 had a significant effect on levels of expression during infection. Therefore, these studies suggest that TATA box and the Inr are the only cis -acting elements required to achieve optimal expression of gC, and that the high levels of late-gene transcription may be largely due to the induction by ICP4, functioning through the Inr element.