title: Transcriptomic and Epigenetic Profiling of the Lung of Influenza-Infected Pigs: A Comparison of Different Birth Weight and Susceptibility Groups.
abstract: Influenza viruses are a common cause of respiratory disease in swine. Infections range in severity from asymptomatic to causing significant morbidity. The main objective of this study was to compare lung transcriptomic and epigenetic responses to influenza infection in pigs from high or low birth weight litters. The latter is a potential indicator of intrauterine growth restriction, a significant risk factor for prenatal programming effects. Individual pigs from high (HBW) or low birth weight (LBW) litters (n = 17) were inoculated with influenza A virus and euthanized 48 hours later. Lesion severity and viral loads were assessed as previously described. The transcriptional response to infection in LBW and HBW groups (n = 16) was assessed by microarray. A separate analysis of pigs classified as 'Resilient' (RES) or 'Susceptible' (SUS) (n = 6) on the basis of severity of lung pathology was also conducted. Eight genes were confirmed as differentially expressed for the birth weight comparison, including three antiviral genes with lower expression in LBW: ISG15, OAS1, and OAS2 (P<0.05). The promoter region methylation status of these three genes was assessed for each birth weight group, and no differences were found. These expression data are consistent with our previous finding that LBW pigs had less severe lesion scores and a trend towards lower viral titres in lung than the HBW cohort. The SUS v RES comparison identified 91 differentially expressed genes (FDR<0.05) that were enriched with functional annotation terms and pathways associated with inflammation. The cytokine genes IL6, IL8, and CCL2 were all upregulated in SUS pigs, and may have driven disease severity in these animals. In conclusion, this study found no evidence that the transcriptional immune response to influenza was adversely affected by low litter birth weight, but did identify several candidate genes for driving disease pathology.
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Wilkinson
authors.affiliation: Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Rayna E
authors.initials: RE
authors.lastname: Gunvaldsen
authors.affiliation: Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Detmer
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Dyck
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Walter T
authors.initials: WT
authors.lastname: Dixon
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: George R
authors.initials: GR
authors.lastname: Foxcroft
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Plastow
authors.affiliation: Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: John C S
authors.initials: JC
authors.lastname: Harding
mesh_terms: D000818:Animals; D001724:Birth Weight; D044127:Epigenesis, Genetic; D015870:Gene Expression; D007113:Immunity, Innate / Q000235:genetics; D008098:Litter Size; D008168:Lung / Q000378:metabolism* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000821:virology; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000821:virology; D059467:Transcriptome; D019562:Viral Load