title: Distinct functional enrichment of transcriptional signatures in pigs with high and low IFN-gamma responses after vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV).
abstract: Little is known about the host factor in the response to PRRSV vaccination. For this purpose, piglets were immunized with a commercial PRRSV-live vaccine and classified as high responders (HR) or low responders (LR) as regards to the frequencies of virus-specific IFN-γ-secreting cells. Six weeks post vaccination, PBMCs isolated from three individuals with the most extreme responses in each HR and LR groups and 3 unvaccinated controls, were either stimulated with phytohaemagglutinin, challenged with the vaccine or mock treated for 24 h, prior conducting transcriptional studies, gene ontology and pathway analyses. The LR group had very low neutralizing antibody levels and showed a higher number of down-regulated transcripts compared with the HR group (FDR < 0.2, P < 0.001). Down-regulated genes encoded chemoattractants, proinflammatory cytokines and the interferon-inducible GBP family, and showed enrichment in wounding (FDR < 3.6E-13), inflammation (FDR < 8E-12), defence (FDR < 8.7E-09) and immunity (FDR < 7.6E-08), suggesting immune response impairment. In the HR group, down-regulated genes were involved in protein transport (FDR < 4.77E-03), locomotory behavior (FDR < 5.47E-3), regulation of protein localization (FDR < 1.02E-02), and regulation of TNF superfamily member 15 and miR181. In contrast, the HR group presented up-regulated transcripts associated with wounding (FDR < 4.95). Moreover, IFN-γ was predicted to be an inhibited upstream regulator since IFN-γ pathways were associated with higher number of down-regulated genes in the LR (n = 40) than the HR (n = 10). Divergent responses to PRRSV-vaccination may be the result of the genetic background of the host.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: Tahar
authors.initials: T
authors.lastname: Ait-Ali
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA)- IRTA, Campus de la Universitat Autònoma de Barcelona (UAB), 08193, Cerdanyola del Valles, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Díaz
authors.affiliation: Virology Department, Animal and Plant Health and Agency, Addlestone, KT15 3NB, UK.|Department of Pathology and Pathogen Biology, Royal Veterinary College, Hatfield, AL9 7TA, UK.
authors.forename: Ferran
authors.initials: F
authors.lastname: Soldevila
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA)- IRTA, Campus de la Universitat Autònoma de Barcelona (UAB), 08193, Cerdanyola del Valles, Spain.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Cano
authors.affiliation: Department Sanitat i Anatomia Animals, Faculty of Veterinary, UAB, 08193, Cerdanyola del Valles, Spain.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Wilson
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Giotti
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, EH25 9RG, UK.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Archibald
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA)- IRTA, Campus de la Universitat Autònoma de Barcelona (UAB), 08193, Cerdanyola del Valles, Spain.|Department Sanitat i Anatomia Animals, Faculty of Veterinary, UAB, 08193, Cerdanyola del Valles, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Mateu
authors.affiliation: Centre de Recerca en Sanitat Animal (CReSA)- IRTA, Campus de la Universitat Autònoma de Barcelona (UAB), 08193, Cerdanyola del Valles, Spain. laila.darwich@uab.cat.|Department Sanitat i Anatomia Animals, Faculty of Veterinary, UAB, 08193, Cerdanyola del Valles, Spain. laila.darwich@uab.cat.
authors.forename: Laila
authors.initials: L
authors.lastname: Darwich
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling / Q000662:veterinary*; D056724:Immunity, Humoral / Q000276:immunology; D059425:Interferon-gamma Release Tests / Q000662:veterinary*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology* / Q000378:metabolism; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D013552:Swine; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*
chemical_list: D014765:Viral Vaccines