Olf-1, a neuron-specific transcription factor, can activate the herpes simplex virus type 1-infected cell protein 0 promoter

Herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons of infected individuals. Infected cell protein 0 (ICP0) is important for productive infection and reactivation from latency. Thus, activation of ICP0 expression in neurons is likely to be important for rea ctivation from latency, In a mouse neuroblastoma cell line, ICP0 promoter a ctivity is high compared with other strong viral promoters. In contrast, pr omoter activity is low in non-neuronal cells. DNase I footprinting assays i ndicated that three distinct motifs in the ICP0 promoter are bound by nucle ar factors. One of these motifs contains a binding site for a novel helix-l oop-helix olfactory neuron-specific transcription factor (Olf-1). Gel shift assays and supershift assays using an Olf-1-specific antibody demonstrated that mouse neuroblastoma cells express Olf-1, which is bound to the Olf-1- like site in the ICP0 promoter. Deletion of the putative Olf-1 motif reduce d ICP0 promoter activity more than 5-fold in mouse neuroblastoma cells and prevented trans-activation by an Olf-1 expression vector. We hypothesize th at the Olf-1-binding site activates ICP0 promoter activity in neurons durin g reactivation from latency.