Transcriptional and post-transcriptional controls establish the cascade of herpes simplex virus protein synthesis

Gene expression by herpes simplex virus type 1 (HSV-1) results in the synthesis of three temporal classes of viral proteins. The three classes of viral proteins are expressed in a cascade manner of sequential dependency. The molecular mechanisms that account for the HSV-1 protein synthesis cascade are poorly understood. In order to provide a detailed description of the metabolic levels at which HSV-1 protein synthesis is regulated, we have measured transcription rates and mRNA accumulation levels for 11 HSV-1 genes. These measurements were made over a time-course of infection in the presence or absence of metabolic inhibitors of either viral protein synthesis or viral DNA synthesis. Our observations show that the protein synthesis cascade of HSV-1 is established as a consequence of mechanisms that regulate both the transcription and accumulation of viral messenger RNA.