title: An intronic polymorphism in the porcine IRF7 gene is associated with better health and immunity of the host during Sarcocystis infection, and affects interferon signalling.
abstract: Interferon regulatory factor 7 (IRF7), as a key regulator of type I interferon response, plays an important role during innate response against viral infection. Although well conserved across species, the structure of IRF7 and its function during parasite infection are not well documented in farm animals, such as the pig. To bridge this gap, we have determined the porcine IRF7 gene structure and identified two intronic single nucleotide polymorphisms (SNPs), SNP g.748G>C and SNP g.761A>G, in commercial pig breeds. The distribution of SNP g.761A>G in multiple breeds suggested that it was in Hardy-Weinberg equilibrium and allowed us to map it at the top of SSC2. We found that during Sarcocystis miescheriana infection, the G allele was associated with high lymphocyte levels (P < 0.02), reduced drop in platelet levels (P < 0.002) and IgG1-Th2-dominated response (P < 0.05). This suggests that the G allele was associated with better health and immunity of the host during Sarcocystis infection. Furthermore, we have also provided suggestive evidence that the G allele of SNPc.761A>G enhances the transactivation activity of IRF7, possibly by improving IRF7 transcript splicing of intron-3. These findings would suggest that IRF7, as a transcriptional regulator, is involved in the defence mechanism against a larger spectrum of pathogens, and in more host species, than initially anticipated.
authors.affiliation: The Roslin Institute and Royal School of Veterinary Studies, The University of Edinburgh, Roslin BioCentre, Midlothian, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Brock
authors.forename: A
authors.initials: A
authors.lastname: Broke
authors.forename: O
authors.initials: O
authors.lastname: Matika
authors.forename: A D
authors.initials: AD
authors.lastname: Wilson
authors.forename: J
authors.initials: J
authors.lastname: Anderson
authors.forename: A-C
authors.initials: AC
authors.lastname: Morin
authors.forename: H A
authors.initials: HA
authors.lastname: Finlayson
authors.forename: G
authors.initials: G
authors.lastname: Reiner
authors.forename: H
authors.initials: H
authors.lastname: Willems
authors.forename: S C
authors.initials: SC
authors.lastname: Bishop
authors.forename: A L
authors.initials: AL
authors.lastname: Archibald
authors.forename: T
authors.initials: T
authors.lastname: Ait-Ali
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D050839:Interferon Regulatory Factor-7 / Q000235:genetics*; D007438:Introns / Q000235:genetics; D016014:Linear Models; D008969:Molecular Sequence Data; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012523:Sarcocystosis / Q000235:genetics / Q000662:veterinary*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D034421:Sus scrofa / Q000235:genetics* / Q000276:immunology; D013552:Swine; D013553:Swine Diseases / Q000235:genetics* / Q000469:parasitology*
chemical_list: D017931:DNA Primers; D050839:Interferon Regulatory Factor-7