Porcine cytokines, chemokines and growth factors: 2019 update

Pigs are a major food source worldwide as well as major biomedical models for human physiology and therapeutics. A thorough understanding of porcine immunity is essential to prevent and treat infectious diseases, and develop effective vaccines and therapeutics. The use of pigs as biomedical models is dependent on the growing molecular and immune toolbox. This paper summarizes current knowledge of swine cytokines, chemokines and growth factors, identifying 289 pig proteins, characterizing knowledge of their gene structures and families. It identifies areas in the current swine genome build that need to be clarified. A broad-based literature and vendor search was conducted to identify defined sets of monoclonal and polyclonal antibodies reacting with porcine cytokines, chemokines, growth factors along with availability of cloned recombinant proteins and assays for their quantitation. This process identified numerous reagents that are reportedly reactive with 170 pig cytokines, chemokines, growth factors: 118 have at least one commercial antibody reagent, 66 a cloned recombinant peptide, and 97 with quantitative assays. This affirms the great need to develop and characterize additional reagents. There are panels of reagents for numerous high priority targets that have been essential reagents for characterizing porcine immunity, disease and vaccine responses, and factors regulating development of innate immune responses, polarized macrophages and lymphoid cells including T regulatory cells. Yet there are many areas requiring investment of efforts to more effectively explore the pig immune system. The development of more reagents to understand the complex of cytokines, chemokines, and growth factors will clearly advance these initiatives

Host genetics of response to porcine reproductive and respiratory syndrome in nursery pigs

PRRS is the most costly disease in the US pig industry. While vaccination, biosecurity and eradication effort have had some success, the variability and infectiousness of PRRS virus strains have hampered the effectiveness of these measures. We propose the use of genetic selection of pigs as an additional and complementary effort. Several studies have shown that host response to PRRS infection has a sizeable genetic component and recent advances in genomics provide opportunities to capitalize on these genetic differences and improve our understanding of host response to PRRS. While work is also ongoing to understand the genetic basis of host response to reproductive PRRS, the focus of this review is on research conducted on host response to PRRS in the nursery and grow-finish phase as part of the PRRS Host Genetics Consortium. Using experimental infection of large numbers of commercial nursery pigs, combined with deep phenotyping and genomics, this research has identified a major gene that is associated with host response to PRRS. Further functional genomics work identified the GBP5 gene as harboring the putative causative mutation. GBP5 is associated with innate immune response. Subsequent work has validated the effect of this genomic region on host response to a second PRRSV strain and to PRRS vaccination and co-infection of nursery pigs with PRRSV and PCV2b. A genetic marker near GBP5 is available to the industry for use in selection. Genetic differences in host response beyond GBP5 appear to be highly polygenic, i.e. controlled by many genes across the genome, each with a small effect. Such effects can by capitalized on in a selection program using genomic prediction on large numbers of genetic markers across the genome. Additional work has also identified the genetic basis of antibody response to PRRS, which could lead to the use of vaccine response as an indicator trait to select for host response to PRRS. Other genomic analyses, including gene expression analyses, have identified genes and modules of genes that are associated with differences in host response to PRRS and can be used to further understand and utilize differences in host response. Together, these results demonstrate that genetic selection can be an additional and complementary tool to combat PRRS in the swine industry

Genome-Wide Association and Genomic Prediction for Host Response to Porcine Reproductive and Respiratory Syndrome Virus Infection

Host genetics has been shown to play a role in porcine reproductive and respiratory syndrome (PRRS), which is the most economically important disease in the swine industry. A region on Sus scrofa chromosome (SSC) 4 has been previously reported to have a strong association with serum viremia and weight gain in pigs experimentally infected with the PRRS virus (PRRSV). The objective here was to identify haplotypes associated with the favorable phenotype, investigate additional genomic regions associated with host response to PRRSV, and to determine the predictive ability of genomic estimated breeding values (GEBV) based on the SSC4 region and based on the rest of the genome. Phenotypic data and 60 K SNP genotypes from eight trials of ~200 pigs from different commercial crosses were used to address these objectives. Across the eight trials, heritability estimates were 0.44 and 0.29 for viral load (VL, area under the curve of log-transformed serum viremia from 0 to 21 days post infection) and weight gain to 42 days post infection (WG), respectively. Genomic regions associated with VL were identified on chromosomes 4, X, and 1. Genomic regions associated with WG were identified on chromosomes 4, 5, and 7. Apart from the SSC4 region, the regions associated with these two traits each explained less than 3% of the genetic variance. Due to the strong linkage disequilibrium in the SSC4 region, only 19 unique haplotypes were identified across all populations, of which four were associated with the favorable phenotype. Through cross-validation, accuracies of EBV based on the SSC4 region were high (0.55), while the rest of the genome had little predictive ability across populations (0.09). Traits associated with response to PRRSV infection in growing pigs are largely controlled by genomic regions with relatively small effects, with the exception of SSC4. Accuracies of EBV based on the SSC4 region were high compared to the rest of the genome. These results show that selection for the SSC4 region could potentially reduce the effects of PRRS in growing pigs, ultimately reducing the economic impact of this disease

Quantitative Trait Locus on Sus scrofa Chromosome 4 Associated with Host Response to Experimental Infection with Porcine Reproductive and Respiratory Syndrome Virus

The objective of this study was to conduct a genomewide association study to discover the genetic basis of host response to PRRS virus using data from the PRRS Host Genetics Consortium NPB and PRRS-CAP project. Approximately 1,600 commercial crossbred piglets were experimentally infected with the Porcine Reproductive and Respiratory Syndrome (PRRS) virus. Blood samples and body weights were collected up to 42 days post infection (dpi). Experimental pigs and their parents were genotyped with Illumina’s Porcine 60k BeadChip. Phenotypes analyzed were viral load (VL = area under the curve for log-transformed qRT-PCR based serum virus from 0-21 dpi) and weight gain from 0-42 dpi (WG). Heritabilities estimated using pedigree information were moderate at 0.41 for VL and 0.29 for WG. A 1 Mb region on Sus scrofa chromosome (SSC) 4 was found to be associated with VL and WG and explained a substantial amount of genetic variation. The frequency of the favorable allele for the most significant single nucleotide polymorphism (SNP) was 0.15. These results show that there is a host genetic component to PRRS virus infection and that there is room for genetic improvement

Report from the Second International Symposium on Animal Genomics for Animal Health: Critical Needs, Challenges and Potential Solutions

The second International Symposium on Animal Genomics for Animal Health held in Paris, France 31 May-2 June, 2010, assembled more than 140 participants representing research organizations from 40 countries. The symposium included a roundtable discussion on critical needs, challenges and opportunities, and a forward look at the potential applications of animal genomics in animal health research. The aim of the roundtable discussion was to foster a dialogue between scientists working at the cutting edge of animal genomics research and animal health scientists. Importantly, stakeholders were included to provide input on priorities and the potential value of animal genomics to the animal health community. In an effort to facilitate the roundtable discussion, the organizers identified four priority areas to advance the use of genome-enabled technologies in animal health research. Contributions were obtained through open discussions and a questionnaire distributed at the start of the symposium. This report provides the outcome of the roundtable discussion for each of the four priority areas. For each priority, problems are identified, including potential solutions and recommendations. This report captures key points made by symposium participants during the roundtable discussion and serves as a roadmap to steer future research priorities in animal genomics research

Factors Associated with N-specific IgG Response in Piglets Experimentally Infected with Porcine Reproductive and Respiratory Syndrome Virus

This study examined serum porcine reproductive and respiratory syndrome virus (PRRSV) N protein-specific IgG levels from sera collected from 464 Large White-Landrace commercial crossbred piglets from three separate experimental infection trials with PRRSV isolate NVSL-97- 7895. IgG levels at 42 days post infection (dpi) were measured by fluorescent microsphere immunoassay, herein referred to as total antibody (tAb) response. tAb levels were assessed for an association with different disease-related traits, the presence of a heritable genetic component, and for genomic regions associated with tAb response. tAb response was negatively associated with viral load (VL) and weight gain from 28-42 dpi (WG) and positively associated with virus rebound (REB) and neutralizing antibody (nAb) levels. Furthermore, tAb response had a heritable genetic component, with a major QTL located on chromosome 7 in the major histocompatibility complex (MHC), whereby heterozygous individuals had a lower tAb response and increased weight gain from 28-42 dpi. These results suggest that genetic selection for tAb response may be useful for selecting for pigs that have increased resistance or reduced susceptibility to PRRSV