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Genome‐wide analysis of TNF ‐alpha response in pigs challenged with porcine circovirus 2b
Author(s) -
Kreikemeier C. A.,
Engle T. B.,
Lucot K. L.,
Kachman S. D.,
Burkey T. E.,
Ciobanu D. C.
Publication year - 2015
Publication title -
animal genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.756
H-Index - 81
eISSN - 1365-2052
pISSN - 0268-9146
DOI - 10.1111/age.12262
Subject(s) - biology , viremia , porcine circovirus , single nucleotide polymorphism , haplotype , immune system , circovirus , virology , tumor necrosis factor alpha , genotype , genetic variation , immunology , antibody , genetics , gene , virus
Summary 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 ( PCV 2) 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 PCV 2‐infected pigs. In this study, we analyzed phenotypic and genetic relationships between TNF ‐ α protein levels, a potential indicator of predisposition to PCV 2 co‐infection, and PCV 2 susceptibility. Following experimental challenge with PCV 2b, 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 SNP s explained 73.9% of the variation in TNF ‐ α at 21 dpi. Major SNP s were identified on SSC 8, SSC 10 and SSC 14. Haplotypes based on SNP s from a SSC 8 (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 PCV 2 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.