title: Genome-wide analysis of TNF-alpha response in pigs challenged with porcine circovirus 2b.
abstract: Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine with a role in activating adaptive immunity to viral infections. By inhibiting the capacity of plasmacytoid dendritic cells to produce interferon-α and TNF-α, porcine circovirus 2 (PCV2) limits the maturation of myeloid dendritic cells and impairs their ability to recognize viral and bacterial antigens. Previously, we reported QTL for viremia and immune response in PCV2-infected pigs. In this study, we analyzed phenotypic and genetic relationships between TNF-α protein levels, a potential indicator of predisposition to PCV2 co-infection, and PCV2 susceptibility. Following experimental challenge with PCV2b, TNF-α reached the peak at 21 days post-infection (dpi), at which time a difference was observed between pigs that expressed extreme variation in viremia and growth (P < 0.10). A genome-wide association study (n = 297) revealed that genotypes of 56,433 SNPs explained 73.9% of the variation in TNF-α at 21 dpi. Major SNPs were identified on SSC8, SSC10 and SSC14. Haplotypes based on SNPs from a SSC8 (9 Mb) 1-Mb window were associated with variation in TNF-α (P < 0.02), IgG (P = 0.05) and IgM (P < 0.13) levels at 21 dpi. Potential overlap of regulatory mechanisms was supported by the correlations between genomic prediction values of TNF-α and PCV2 antibodies (21 dpi, r > 0.22), viremia (14-21 dpi, P > 0.29) and viral load (r = 0.31, P < 0.0001). Characterization of the QTL regions uncovered genes that could influence variation in TNF-α levels as well as T- and B-cell development, which can affect disease susceptibility.
authors: Animal Science Department, University of Nebraska, Lincoln, NE, 68583, USA.
authors: C A
authors: CA
authors: Kreikemeier
authors: T B
authors: TB
authors: Engle
authors: K L
authors: KL
authors: Lucot
authors: S D
authors: SD
authors: Kachman
authors: T E
authors: TE
authors: Burkey
authors: D C
authors: DC
authors: Ciobanu
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018173:Circoviridae Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D017925:Circovirus; D055106:Genome-Wide Association Study; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D034421:Sus scrofa / Q000235:genetics* / Q000276:immunology / Q000821:virology; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000276:immunology; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D014409:Tumor Necrosis Factor-alpha
keywords: immunity; porcine circovirus 2; swine; tumor necrosis factor alpha