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

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dc.contributor.author Schroyen, M.
dc.contributor.author Eisley, C.
dc.contributor.author Koltes, J. E.
dc.contributor.author Fritz-Waters, E.
dc.contributor.author Choi, I.
dc.contributor.author Plastow, G. S.
dc.contributor.author Guan, L. L.
dc.contributor.author Stothard, P.
dc.contributor.author Bao, H.
dc.contributor.author Kommadath, A.
dc.contributor.author Reecy, J. M.
dc.contributor.author Lunney, J. K.
dc.contributor.author Rowland, Raymond R.
dc.contributor.author Dekkers, J. C. M.
dc.date.accessioned 2016-09-20T17:34:01Z
dc.date.available 2016-09-20T17:34:01Z
dc.date.issued 2016-03-08
dc.identifier.uri http://hdl.handle.net/2097/34056
dc.description Citation: Schroyen, M., Eisley, C., Koltes, J. E., Fritz-Waters, E., Choi, I., Plastow, G. S., . . . Tuggle, C. K. (2016). 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, 16. doi:10.1186/s12864-016-2547-z
dc.description Additional Authors: Tuggle, C. K.
dc.description.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.
dc.relation.uri https://doi.org/10.1186/s12864-016-2547-z
dc.rights Attribution 4.0 International (CC BY 4.0)
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Pig
dc.subject Prrs Virus
dc.subject Rna-Seq
dc.subject Wur
dc.subject Gbp5
dc.subject Ion Transport
dc.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
dc.type Article
dc.date.published 2016
dc.citation.doi 10.1186/s12864-016-2547-z
dc.citation.issn 1471-2164
dc.citation.jtitle Bmc Genomics
dc.citation.spage 16
dc.citation.volume 17
dc.contributor.authoreid rrowland


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