Quantitative Trait Loci Associated with the Immune Response to a Bovine Respiratory Syncytial Virus Vaccine

Abstract

Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501) which was genotyped for 165 microsatellite markers (covering all autosomes) to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV) specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL) on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected. Heifers from the same population (n = 195) were subsequently immunised with a 40-mer Foot-and-Mouth Disease Virus peptide (FMDV) in a previous publication. Several of these QTL associated with the FMDV traits had overlapping peak positions with QTL in the current study, including the QTL on BTA23 which included the bovine Major Histocompatibility Complex (BoLA), and QTL on BTA9 and BTA24, suggesting that the genes underlying these QTL may control responses to multiple antigens. These results lay the groundwork for future investigations to identify the genes underlying the variation in clearance of maternal antibody and response to vaccination.

The molecular pathways underlying host resistance and tolerance to pathogens

“…For example, young cattle infected with bovine respiratory syncytial virus (BRSV), show considerable lung pathology that appears to be linked to an influx of immune cells, whereas infection of bovine epithelial cells in vitro with BRSV do not show cytopathology (Valarcher and Taylor, 2007). Although there is considerable literature to suggest that, there is a genetic component to the response to BRSV (Glass et al, 2010, 2012a; Leach et al, 2012), whether this relates to resistance and/or tolerance is unclear. Additionally, an ability to protect the host from damage caused by pathogen derived toxicity could also be a component of a tolerance phenotype (Medzhitov, 2009).…”

“…Furthermore, it is easier to measure some parameters than others e.g., systemic antibody responses can be monitored from small stored serum samples, unlike localized cellular responses in large numbers of animals. Yet for many infections, protective mechanisms involve diverse immune responses that also differ across time (Glass et al, 2012a,b; Leach et al, 2012). Additionally, the relationship between immune measures and protection or indeed, “fitness” is usually not clear (Graham et al, 2010; Schneider, 2011).…”

Heterogeneity in the Antibody Response to Foot-and-Mouth Disease Primo-vaccinated Calves

“…The induction of neutralizing antibodies is the mechanism most frequently related to protection against FMDV (Barnett and Carabin, 2002;Golde et al, 2005;Orsel et al, 2005;Cox et al, 2006Cox et al, , 2007Maradei et al, 2008;Robiolo et al, 2010), and a number of reports have provided indepth information about the genetic control of humoral responses in cattle (O'Neill et al, 2006;Minozzi et al, 2010;Glass et al, 2011;Leach et al, 2012). Previous work has shown MHC-based restrictions to FMDV-derived antigens in cattle.…”

Mapping complex traits as a dynamic system

“…Wolf et al [169] integrated genetic mapping and structural equation models to detect a QTL for flowering time in focal plants that pleiotropically affects the expression of developmental traits in the neighbor plants. Also, there has been a body of other literature that reports the detection of QTLs for phenotypic traits related to interspecific interactions, such as immune response [80], tolerance to herbivory [160], mate recognition [130], or predator-defense traits [96], by using conventional mapping approaches.…”