Expression of the approximately 70 herpes simplex virus type 1 (HSV-1) genes is regulated primarily at the level of mRNA transcription, and can be conveniently divided into three phases based on the temporal order of mRNA synthesis. Immediate-early genes are expressed soon after virus infection, and their gene products are required for the expression of early genes, many of whose gene products are involved in viral DNA replication. Expression of viral late genes requires viral DNA replication and functional immediate-early gene products. Understanding the regulation of HSV gene expression, and the function of individual gene products, is necessary if approaches are to be developed for control of herpesvirus infections. This research project is designed to study the temporal expression of herpes simplex type 1 late genes, those genes expressed only after viral DNA replication. We have done extensive mutational analysis of the promoter regions of several gylcoprotein genes and have identified three separate sequence elements that are involved in expression. These elements are interchangeable from one promoter to another, and include a TATA element, an initiator-like region at the start of transcription, and a downstream element necessary for maximal expression. Recent work indicates that the TATA element and the initiator element are part of the basal late promoter, but that the downstream element is only active during DNA replication. Currently, we are investigating the link between ongoing replication and the downstream element, and the similarity between the initiator region of HSV late genes and other eukaryotic initiators.
