Productive infection and bICP0 early promoter activity of bovine herpesvirus 1 are stimulated by E2F1.
Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen of cattle. Like other members of the subfamily Alphaherpesvirinae, BoHV-1 establishes latency in sensory neurons and has the potential to reactivate from latency. Dexamethasone (DEX) treatment of latently infected calves or rabbits consistently leads to reactivation from latency. The BoHV-1 transcript encoding the infected cell protein 0 (bICP0) is consistently detected during reactivation from latency, in part because the bICP0 early promoter is activated by DEX. During DEX-induced reactivation from latency, cyclin expression is stimulated in infected sensory neurons. Cyclin-dependent kinase activity phosphorylates Rb (retinoblastoma tumor suppressor gene product) family proteins and consequently releases the E2F family of transcription factors, suggesting that E2F family members stimulate productive infection and/or reactivation from latency. In this study, we provide evidence that repression of E2F1 by a specific small interfering RNA (siRNA) reduced productive infection approximately 5-fold. E2F1 or E2F2 stimulated bICP0 early promoter activity at least 100-fold in transient transfection assays. Two E2F-responsive regions (ERR) were identified within the early promoter, with one adjacent to the TATA box (ERR1) and one approximately 600 bp upstream from the TATA box (ERR2). Mobility shift assays suggested that E2F interacts with ERR1 and ERR2. E2F1 protein levels were increased at late times after infection, which correlated with enhanced binding to a consensus E2F binding site, ERR1, or ERR2. Collectively, these studies suggest that E2F1 stimulates productive infection and bICP0 early promoter activity, in part because E2F family members interact with ERR1 and ERR2.
Workman
Aspen
A
Department of Veterinary and Biomedical Sciences and Nebraska Center for Virology, University of Nebraska, Lincoln Fair Street at East Campus Loop, Lincoln, NE 68583-0905, USA.
Jones
Clinton
C
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002460:Cell Line; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D055785:Gene Knockdown Techniques; D007242:Herpesvirus 1, Bovine / Q000502:physiology*; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering; D011817:Rabbits; D011960:Receptors, Estrogen / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*; D014775:Virus Activation; D000097983:ERRalpha Estrogen-Related Receptor
D050687:E2F1 Transcription Factor; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; D000097983:ERRalpha Estrogen-Related Receptor; C098925:Esrrb protein, mouse; C086729:bICP0 protein, Bovine herpesvirus 1
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