title: Bioinformatic analyses in early host response to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) reveals pathway differences between pigs with alternate genotypes for a major host response QTL.
abstract: BACKGROUND
  A region on Sus scrofa chromosome 4 (SSC4) surrounding single nucleotide polymorphism (SNP) marker WUR10000125 (WUR) has been reported to be strongly associated with both weight gain and serum viremia in pigs after infection with PRRS virus (PRRSV). A proposed causal mutation in the guanylate binding protein 5 gene (GBP5) is predicted to truncate the encoded protein. To investigate transcriptional differences between WUR genotypes in early host response to PRRSV infection, an RNA-seq experiment was performed on globin depleted whole blood RNA collected on 0, 4, 7, 10 and 14 days post-infection (dpi) from eight littermate pairs with one AB (favorable) and one AA (unfavorable) WUR genotype animal per litter.
  
  
  RESULTS
  Gene Ontology (GO) enrichment analysis of transcripts that were differentially expressed (DE) between dpi across both genotypes revealed an inflammatory response for all dpi when compared to day 0. However, at the early time points of 4 and 7dpi, several GO terms had higher enrichment scores compared to later dpi, including inflammatory response (p < 10(-7)), specifically regulation of NFkappaB (p < 0.01), cytokine, and chemokine activity (p < 0.01). At 10 and 14dpi, GO term enrichment indicated a switch to DNA damage response, cell cycle checkpoints, and DNA replication. Few transcripts were DE between WUR genotypes on individual dpi or averaged over all dpi, and little enrichment of any GO term was found. However, there were differences in expression patterns over time between AA and AB animals, which was confirmed by genotype-specific expression patterns of several modules that were identified in weighted gene co-expression network analyses (WGCNA). Minor differences between AA and AB animals were observed in immune response and DNA damage response (p = 0.64 and p = 0.11, respectively), but a significant effect between genotypes pointed to a difference in ion transport/homeostasis and the participation of G-coupled protein receptors (p = 8e-4), which was reinforced by results from regulatory and phenotypic impact factor analyses between genotypes.
  
  
  CONCLUSIONS
  We propose these pathway differences between WUR genotypes are the result of the inability of the truncated GBP5 of the AA genotyped pigs to inhibit viral entry and replication as quickly as the intact GBP5 protein of the AB genotyped pigs.
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. schroyen@iastate.edu.
authors.forename: Martine
authors.initials: M
authors.lastname: Schroyen
authors.affiliation: Department of Statistics, Iowa State University, 1121 Snedecor Hall, Ames, IA, 50011, USA. cje2718@gmail.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Eisley
authors.affiliation: Department of Animal Science, University of Arkansas, AFLS B106D, Fayetteville, AR, 72701, USA. koltes@uark.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Koltes
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. ercfrtz@iastate.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Fritz-Waters
authors.affiliation: USDA-ARS, BARC, APDL, Bldg.1040, Beltsville, MD, 20705, USA. igseochoi@gmail.com.
authors.forename: Igseo
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. plastow@ualberta.ca.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Plastow
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. lguan@ualberta.ca.
authors.forename: Leluo
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. stothard@ualberta.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Stothard
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. bao1@ualberta.ca.
authors.forename: Hua
authors.initials: H
authors.lastname: Bao
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada. kommadat@ualberta.ca.
authors.forename: Arun
authors.initials: A
authors.lastname: Kommadath
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. jreecy@iastate.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Reecy
authors.affiliation: USDA-ARS, BARC, APDL, Bldg.1040, Beltsville, MD, 20705, USA. joan.lunney@ars.usda.gov.
authors.forename: Joan K
authors.initials: JK
authors.lastname: Lunney
authors.affiliation: College of Veterinary Medicine, Kansas State University, K-231 Mosier Hall, Manhattan, KS, 66506, USA. browland@vet.k-state.edu.
authors.forename: Robert R R
authors.initials: RR
authors.lastname: Rowland
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. jdekkers@iastate.edu.
authors.forename: Jack C M
authors.initials: JC
authors.lastname: Dekkers
authors.affiliation: Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA. cktuggle@iastate.edu.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Tuggle
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology; D019295:Computational Biology; D016207:Cytokines / Q000276:immunology; D004249:DNA Damage; D019204:GTP-Binding Proteins / Q000235:genetics*; D005838:Genotype; D058847:Inflammasomes / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics* / Q000276:immunology; D019316:Porcine respiratory and reproductive syndrome virus; D017423:Sequence Analysis, RNA; D034421:Sus scrofa / Q000235:genetics* / Q000276:immunology / Q000821:virology; D013552:Swine; D059467:Transcriptome; D014766:Viremia / Q000235:genetics / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D058847:Inflammasomes; D019204:GTP-Binding Proteins