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

Location: Virus and Prion Research

Title: Antiviral potency and functional novelty of porcine interferon-omega subtype

item SHIELDS, LAUREN - Tennessee State University
item LIU, Q - Kansas State University
item MA, WEN-JUN - Kansas State University
item Miller, Laura
item SANG, YONGMING - Tennessee 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: Shields, L.E., Liu, Q., Ma, W., Miller, L.C., Sang, Y. 2018. Antiviral potency and functional novelty of porcine interferon-omega subtype [abstract]. Research Workers in Animal Diseases Conference Proceedings. p. 226.

Interpretive Summary:

Technical Abstract: Objective: The expansion of IFN-omega molecular diversity in pigs represents a signature event of type I IFN evolution in mammalian species. Focusing on the antiviral and inflammatory regulation of IFN-omega members, our goal is the family-wide characterization of porcine innate immune IFNs for their therapeutic potential and functional spectrum, which will be determined against two RNA viruses (PRRSV and SIV) that highly affect swine and potentially human health. Methods: Quantitative RT-PCR assays and probe-based IFN detection were used for expression analyses. IFN bioassay and antiviral titration were used to analyze IFN activity. For inflammatory regulation, we will treat lung tissue or cell cultures with IFN peptides, and determine the consequent inflammatory responses per pathological examination and inflammatory cytokine detection. An animal test will be implemented using the IFN candidates verified through in vitro analysis. We will examine the novel features of porcine IFN-omega signaling including extracellular and intracellular interaction/dependence with receptor subunits, IFNAR1 and IFNAR2. Results: We have evolutionarily defined the porcine IFN family, and preliminarily demonstrated that porcine IFN-omega subtype has evolved several novel features including, (1) a signature multi-gene subtype expanding particularly in bats and ungulates, (2) emerging isoforms that have much higher antiviral potency than typical IFN-alpha, (3) cross-species high antiviral (but little antiproliferative) activity in cells of humans and other mammalian species, and (4) potential action through non-canonical signaling pathways. Conclusions: Molecular evolution analyses across 155 animal genomes show that pigs have the largest and an expanding type I IFN complex consisting of nearly 60 functional genes that encode seven IFN subtypes including multigene subtypes of IFN-alpha and -omega. Compared with typical IFN-alpha and -beta subtypes, the unconventional IFN-omega subtype has barely been investigated. After molecularly defining the porcine IFN family, we showed that porcine IFN-omega subtype has evolved several novel functional features with respect to antiviral and inflammatory regulation. Supported by grants from USDA (NIFA AFRI 2013-67015-26517, and particularly NIFA AFRI 2018-67016-28313)