Immediate-early gene regulation in herpes simplex virus

Abstract

All α herpesviruses have a rather similar immediate-early gene organization and gene regulation pathway, which differs dramatically from those of the β (CMV) and γ (EBV) subclasses of herpesviruses. Herpes simplex virus (HSV), the prototype for α herpesviruses, encodes a virion transcription factor (VP16) that complexes with the cellular Oct-1 DNA binding protein in newly-infected cells and specifically activates several viral immediate-early promoters. Subsequently, three viral nuclear transactivators (IE175, IE110 and IE63) act together, at both the transcriptional and post-transcriptional levels, to maximize expression of the downstream cascade of delayed-early and late genes. IE175 is a DNA-binding protein that can also specifically down-regulate both its own and one or more latent state promoters. During maintenance of the latent state in sensory neurons, viral IE expression is kept shut-down by a variety of negative factors that probably include antisense mechanisms. Finally, the IE110 protein appears to be a key alternative trigger of lytic cycle events for reactivation in the absence of the virion factor.