Genome‐wide analysis of TNF‐alpha response in pigs challenged with porcine circovirus 2b. (23rd January 2015)

• Record Type: Journal Article
• Authors: Kreikemeier, C. A.; Engle, T. B.; Lucot, K. L.; Kachman, S. D.; Burkey, T. E.; Ciobanu, D. C.
• Is Part Of: Animal genetics. Volume 46:Number 2(2015:Apr.)
• Page Start: 205
• Page End: 208
• Publication Date: 2015-01-23
• Subjects: Animal genetics -- Periodicals; 572.8
• DOI: 10.1111/age.12262
• Languages: English
• ISSNs: 0268-9146

Abstract

<abstract abstract-type="main" id="age12262-abs-0001"> <title>Summary</title> <p>Tumor necrosis factor alpha (TNF‐<italic>α</italic>) 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‐<italic>α</italic> and TNF‐<italic>α</italic>, 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‐<italic>α</italic> protein levels, a potential indicator of predisposition to PCV2 co‐infection, and PCV2 susceptibility. Following experimental challenge with PCV2b, TNF‐<italic>α</italic> 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 (<italic>P </italic>< 0.10). A genome‐wide association study (<italic>n </italic>=<italic> </italic>297) revealed that genotypes of 56 433 SNPs explained 73.9% of the variation in TNF‐<italic>α</italic> 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‐<italic>α</italic> (<italic>P </italic><<italic> </italic>0.02), IgG (<italic>P </italic>=<italic> </italic>0.05) and IgM (<italic>P </italic><<italic> </italic>0.13) levels at 21 dpi. Potential overlap of regulatory mechanisms was supported by the correlations between genomic prediction values of TNF‐<italic>α</italic> and PCV2 antibodies (21 dpi, <italic>r </italic>><italic> </italic>0.22), viremia (14–21 dpi, <italic>P </italic>><italic> </italic>0.29) and viral load (<italic>r </italic>=<italic> </italic>0.31, <italic>P </italic><<italic> </italic>0.0001). Characterization of the QTL regions uncovered genes that could influence variation in TNF‐<italic>α</italic> levels as well as T‐ and B‐cell development, which can affect disease susceptibility.</p> </abstract>