The cellular transcription factor, CCAAT enhancer-binding protein alpha (C/EBP-alpha), has the potential to activate the bovine herpesvirus 1 immediate-early transcription unit 1 promoter.

Following acute infection, bovine herpesvirus-1 (BHV-1) establishes a lifelong latent infection in sensory neurons of trigeminal ganglia. BHV-1 periodically reactivates from latency and is shed as infectious virus. The latency-related (LR) gene is abundantly expressed in trigeminal ganglia of infected calves, and proteins encoded by the LR gene are necessary for reactivation from latency. We previously demonstrated that a novel LR protein interacts with a host transcription factor, CCAAT enhancer-binding protein alpha (C/EBPalpha). C/EBPalpha increases plaque-forming efficiency when cotransfected with BHV-1 DNA and its expression is induced in neurons during reactivation from latency (Meyer et al, 2007, J Virol 81: 59-67). The ability of C/EBPalpha to bind DNA is necessary for stimulating productive infection, suggesting C/EBPalpha stimulates viral transcription. We tested whether C/EBPalpha could trans-activate the BHV-1 immediate early transcription unit 1 (IEtu1) promoter because the IEtu1 promoter activates expression of two viral genes (bICP0 and bICP4) that stimulate producitve infection. In the current study, We demonstrate that C/EBPalpha and the BHV-1 trans-inducing factor (bTIF) synergistically trans-activate IEtu1 promoter activity. However, bICP0 and C/EBPalpha did not synergistically trans-activate IEtu1 promoter activity. Deletion of IEtu1 promoter sequences demonstrated that C/EBPalpha by itself could trans-activate a truncated IEtu1 promoter, suggesting sequences in the distal region of the IEtu1 promoter negatively regulate C/EBPalpha activtiy. These studies suggest that C/EBPalpha stimulates productive infection and reactivation from latency, in part, by cooperating with bTIF to activate IEtu1 promoter activity.