Location: Virus and Prion Research
Project Number: 5030-32000-108-25-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Dec 9, 2013
End Date: Aug 31, 2017
Correlate the activation status with antiviral responses in porcine monocytic innate immune cells, and to functionally modulate them as a cellular adjuvant/vaccine for ideal antiviral potentiation in vivo. To our knowledge, few studies have been done to molecularly and functionally categorize porcine monocytic innate immune cells according to the activation status paradigm emerging in other species. Understanding the relationships of activation status and antiviral states not only extends the activation paradigm of these cells but also integrates innate immune responses with several aspects of inflammation, tissue repair and overall antimicrobial activity. This is important because most porcine reproductive and respiratory syndrome (PRRS) virus infections are syndromes complicated with co-infection from pathogens of other phyla. Therefore, integration of conventional activation status and antiviral states provides a framework for potentiation of overall immune response to PRRS diseases. Thus, through therapeutic manipulation of these cells pertaining to their activation and antiviral states, we ultimately will develop a cellular adjuvant/vaccine with enhanced antiviral efficacy for PRRS.
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.