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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
BMC Genomics
  • Martine Schroyen, Iowa State University
  • Christopher Eisley, Iowa State University
  • James E. Koltes, University of Arkansas, Fayetteville
  • Eric Fritz-Waters, Iowa State University
  • Igseo Choi, U.S. Department of Agriculture
  • Graham S. Plastow, University of Alberta
  • Leluo Guan, University of Alberta
  • Paul Stothard, University of Alberta
  • Hua Bao, University of Alberta
  • Arun Kommadath, University of Alberta
  • James M. Reecy, Iowa State University
  • Joan K. Lunney, U.S. Department of Agriculture
  • Robert R. R. Rowland, Kansas State University
  • Jack C. M. Dekkers, Iowa State University
  • Christopher K. Tuggle, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
1-1-2016
DOI
10.1186/s12864-016-2547-z
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.

Conclusion: 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.

Comments

This article is published as Schroyen, Martine, Christopher Eisley, James E. Koltes, Eric Fritz-Waters, Igseo Choi, Graham S. Plastow, Leluo Guan et al. "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." BMC genomics 17 (2016): 196. doi: 10.1186/s12864-016-2547-z.

Rights
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
Language
en
File Format
application/pdf
Citation Information
Martine Schroyen, Christopher Eisley, James E. Koltes, Eric Fritz-Waters, et al.. "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" BMC Genomics Vol. 17 (2016) p. 196
Available at: http://works.bepress.com/james_reecy/118/