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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #355595

Research Project: Antiviral Potency and Functional Novelty of Porcine Interferon-Omega Subtype

Location: Virus and Prion Research

Title: Antiviral regulation underlying the activation status of porcine monocytic innate immune cells

item SANG, YONGMING - Tennessee State University
item Miller, Laura
item SHIELDS, LAUREN - Tennessee State University
item FLEMING, DAMARIUS - Orise Fellow
item BLECHA, FRANK - Kansas State University

Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/26/2018
Publication Date: 12/1/2018
Citation: Sang, Y., Miller, L.C., Shields, L.E., Fleming, D.S., Blecha, F. 2018. Antiviral regulation underlying the activation status of porcine monocytic innate immune cells [abstract]. Research Workers in Animal Diseases Conference Proceedings. abstract No. 302.

Interpretive Summary:

Technical Abstract: Objective: The general objective of this project is to integrate activation status with antiviral responses in porcine monocytic cells, which include blood monocytes, tissue macrophages and monocyte-derived dendritic cells (mDCs), and thereby to functionally modulate for a vaccine design to protect PRRSV infection. Methods: PRRSV-infected or mock-infected cells were used for transcriptomic profiling of signature genes and gene responsive pathways. The cells were further phenotypically analyzed using ELISA for cytokines and flow cytometry for cell markers. A PRRSV-P129 cDNA infectious clone was manipulated as vaccine backbone to express porcine type I interferons (IFN) accompanying the MLV replication. Cell and animal tests were performed to evaluate the vaccine effect in comparison to a commercial vaccine. Results: The activation status of porcine monocytic cells (particularly macrophages and mDCs) were directly involved in response to PRRSV infection; and signature gene responsive pathways involving both immune and metabolic aspects were pinpointed in our omics datasets. Based on this, we developed a vaccine formula via incorporated expression of effective IFNs using a virus reverse-genetic tool. Several vaccine backbones with replication-competent expression of effective IFNs exerted expected antiviral efficacy in porcine cells, and especially some vaccine candidates were more effective to protect pigs from a field-isolate challenge with lower viral load and fever compared with a commercial vaccine. Conclusions: (1) The activation status of porcine monocytic cells interact with both PRRSV infection and corresponding antiviral responses; (2) Antiviral states are connected with the other activation statuses of the porcine monocytic cells; (3) Some signature gene responsive pathways especially of those in IFN-signaling and lipid-metabolic pathways are critical in mediation of PRRSV infection; and (4) The MLV vaccine candidates with IFN-producing characteristic is promising for stimulating better anti-PRRSV immunity against PRRSV field-isolates. Supported by grants from USDA (NIFA AFRI 2013-67015-21236 and NIFA AFRI 2013-67015-26517)