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 life-long 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 reactivation from latency. In a mouse neuroblastoma cell line, ICP0 promoter activity is high compared with other strong viral promoters. In contrast, promoter activity is low in non-neuronal cells. DNase I footprinting assays indicated that three distinct motifs in the ICP0 promoter are bound by nuclear factors. One of these motifs contains a binding site for a novel helix-loop-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 reduced ICP0 promoter activity more than 5-fold in mouse neuroblastoma cells and prevented trans-activation by an Olf-1 expression vector. We hypothesize that the Olf-1-binding site activates ICP0 promoter activity in neurons during reactivation from latency.
Devireddy
L R
LR
Center for Biotechnology, Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska 68583-0905, USA.
Jones
C J
CJ
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018259:Herpesvirus 1, Human; D017874:Immediate-Early Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009475:Neurons, Afferent / Q000821:virology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D017735:Virus Latency
D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1