A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis

Abstract

Controlled transcription of animal virus DNAs provides potentially useful models for elucidating the mechanisms which regulate eukaryotic gene expression. The progressive transcription of the herpes simplex virus type 1 (HSV-1) genome has been described previously^1–3. Infection of permissive cells with HSV-1 in the presence of the protein synthesis inhibitor cycloheximide resulted in transcription of a restricted set of virus RNAs, referred to as the immediate early RNAs, which map within certain regions of the virus genome only^3–5. Removal of cycloheximide led to the transcription of additional virus DNA sequences, which were expressed during the normal replicative cycle both at early and late times post-infection (before and after the onset of virus DNA replication, respectively) and which map throughout the virus genome³. Previously, we have described a temperature-sensitive mutant of HSV-1 Glasgow strain 17, ts K, which accumulated only the immediate early RNAs at the non-permissive temperature (NPT)⁵. Transfer of ts K-infected cells from NPT to the permissive temperature (PT), even in the absence of de novo protein synthesis, resulted in transcription of the DNA sequences expressed early and late post-infection⁵. This indicated the persistence at NPT of a non-functional immediate early polypeptide which on transfer to PT regained its function, required for progression from the immediate early to early stage of transcription. Here we demonstrate, by analysing the RNAs made in ts K-infected cells after transfer from PT to the NPT, that this polypeptide's function is required continuously for synthesis of HSV-1 early and late RNAs, thus identifying a control function essential for the expression of early and late HSV genetic information in eukaryotic cells.