Genes controlling vaccine responses and disease resistance to respiratory viral pathogens in cattle

Abstract

Farm animals remain at risk of endemic, exotic and newly emerging viruses. Vaccination is often promoted as the best possible solution, and yet for many pathogens, either there are no appropriate vaccines or those that are available are far from ideal. A complementary approach to disease control may be to identify genes and chromosomal regions that underlie genetic variation in disease resistance and response to vaccination. However, identification of the causal polymorphisms is not straightforward as it generally requires large numbers of animals with linked phenotypes and genotypes. Investigation of genes underlying complex traits such as resistance or response to viral pathogens requires several genetic approaches including candidate genes deduced from knowledge about the cellular pathways leading to protection or pathology, or unbiased whole genome scans using markers spread across the genome.Evidence for host genetic variation exists for a number of viral diseases in cattle including bovine respiratory disease and anecdotally, foot and mouth disease virus (FMDV). We immunised and vaccinated a cattle cross herd with a 40-mer peptide derived from FMDV and a vaccine against bovine respiratory syncytial virus (BRSV). Genetic variation has been quantified. A candidate gene approach has grouped high and low antibody and T cell responders by common motifs in the peptide binding pockets of the bovine major histocompatibility complex (BoLA) DRB3 gene. This suggests that vaccines with a minimal number of epitopes that are recognised by most cattle could be designed. Whole genome scans using microsatellite and single nucleotide polymorphism (SNP) markers has revealed many novel quantitative trait loci (QTL) and SNP markers controlling both humoral and cell-mediated immunity, some of which are in genes of known immunological relevance including the toll-like receptors (TLRs).The sequencing, assembly and annotation of livestock genomes and is continuing apace. In addition, provision of high-density SNP chips should make it possible to link phenotypes with genotypes in field populations without the need for structured populations or pedigree information. This will hopefully enable fine mapping of QTL and ultimate identification of the causal gene(s). The research could lead to selection of animals that are more resistant to disease and new ways to improve vaccine efficacy.

Carbopol improves the early cellular immune responses induced by the modified-life vaccine Ingelvac PRRS® MLV

“…Gene set enrichmentbased approach has been used to develop predictors of human vaccine outcome, suggesting the genetic background as determinant in inducing immune responses (Tan et al, 2014). Evidence for the impact of genetic variation exists also for a number of livestock diseases (Glass et al, 2012 andCordes et al, 2012). In addition to histocompatibility genes, microarray analysis showed transcriptional differences in several immune-related genes between high and low responders (Nino-Soto et al, 2008).…”

Major Histocompatibility Complex-Associated Resistance to Infectious Diseases: The Case of Bovine Leukemia Virus Infection

“…Based on data registered in the Domestic Animal Diversity Information System (DAD-IS) 2015 report [42], 483 mammalian breed populations are recorded as having resistance or tolerance to Not unexpectedly, the high degree of genetic polymorphism in the MHC has been associated with health status, vaccine responsiveness, and production traits in cattle [43][44][45][46][47]. Examples of some studies for which there is documented evidence of MHC association with resistance or susceptibility to disease include mastitis in cattle and sheep [44,48], tick-borne disease [49][50][51], dermatophilosis in cattle [52], enzootic bovine leucosis in cattle and sheep [53][54][55][56], neosporosis in cattle [57], theileriosis in cattle [58], gastrointestinal parasites in sheep [59,60], diarrhea in pigs [61,62], Marek's disease in chicken [63,64], coccidiosis in chicken [65], and coronavirus resistance in chickens [66], among others.…”

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, strong evidence has accumulated that livestock species from birds to mammals, harbor genes that control protective responses to the various classes of pathogen from viruses to complex metazoans such as nematodes (for reviews that comprehensively cover different livestock species and pathogens see e.g., Davies et al, 2009; Mirkena et al, 2010). However, there remains a “phenotype gap” for traits linked to disease resistance and tolerance (Glass et al, 2012a,b). This is partly because host-pathogen interactions are highly complex, involving many different molecules and cell types which interact together over time.…”