Generation of Pseudorabies-resistant Animals by Germ-line Transformation

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To examine the activity of several gene promoters of pseudorabies virus (PRV) in vivo, we have generated transgenic mice expressing transgenes under the control of the viral promoters. Analyses of the tissue specificity of transgene expression demonstrated that the immediate-early gene promoter is neuronal tissue-specific, the early protein 0 gene promoter is a pan-specific and the latency associated transcript gene promoter is a neuron-specific, respectively.In order to assess the antiviral potential of PRV IE180 and a dominant-negative mutant of EP0 in vivo, several transgenic mouse lines expressing IE180 or the dominant-negative mutant of EP0 were generated. Experimental infection to these transgenic mice is now in progress.Herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor receptor family used as a cellular receptor by virion glycoprotein D (gD) of herpes simplex virus (HSV). In order to assess the antiviral potential of HVEM in vivo, three transgenic mouse lines expressing a soluble form of HVEM (HVEMlg) consisting of an extracellular domain of murine HVEM and the Fc portion of human lgG1 were generated. All of the transgenic mouse lines showed marked resistance to HSV-1 infection. To adapt this finding for generation of pseudorabies-resistant animal, we used porcine herpesvirus entry mediator C (HveC). Vero cells were transformed with the chimeric gene expressing a fusion protein consisting of an extracellular domain of porcine HveC and the Fc portion of human lgG1. The transformed cell lines expressing the fusion protein showed marked resistance to PRV infection. Generation of transgenic mice expressing the fusion protein is now in progress. These findings suggest the potential value of the fusion protein in agricultural livestock for enhanced disease resistance to pseudorabies.