Start Date: Dec 09, 2013
End Date: Aug 31, 2017
Activation status of primary cells and ex vivo stimulated cells will be molecularly defined by expression of marker genes and functionally phenotyped for regulation in inflammation and T-cell proliferation. Correlation with antiviral responses will be compared among the subgroups of cells for resistance to viral entrance/replication and to viral suppression in interferon (IFN) production and action. Cell ex vivo manipulation will be conducted by drug/ligand stimulation and virus-vector mediated gene delivery and targeted expression. Provide assistance in conducting all phases of the animal studies using the highly-pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) under BSL3 Ag containment at the National Animal Disease Center, ranging from obtaining institutional permission through euthanasia and necropsy of experimental animals. Conduct experiments to examine gene expression upon infection with porcine reproductive and respiratory syndrome virus (PRRSV) and HP-PRRSV through transcriptomic analysis as described in the project narrative: Aim 1. Systematically characterize the activation status and genome-wide determine signature genes potentially regulating the activation status in porcine monocytic innate immune cells. Aim 2. Correlate cell activation status with PRRSV pathogenicity in ex vivo stimulated cells and in primary cells isolated from virus-infected pigs. Aim 3. Develop a prototypic adjuvant/vaccine system based on functional modulation of activation statuses in porcine monocytic innate immune cells.