A DIO2 missense mutation and its impact on fetal response to PRRSV infection

• Published in: BMC veterinary research 2024-06, Vol.20 (1), p.255-16
• Main Authors: Ko, Haesu, Pasternak, J Alex, Mulligan, Margaret K, Hamonic, Glenn, Ramesh, Naresh, MacPhee, Daniel J, Plastow, Graham S, Harding, John C S
• Format: Article
• Language: English
• Subjects: Animal diseases; Animals; Chromosome 7; Cortisol; Cytokines; Deiodinase; Female; Fetus; Fetus - virology; Fetuses; Gene expression; Gene mutations; Gene polymorphism; Genetic aspects; Genome-wide association studies; Genomics; Genotype; Genotype & phenotype; Genotyping; Haplotypes; Health aspects; Heterozygotes; Hogs; Homozygotes; Hormones; Hypothalamic-pituitary-adrenal axis; Hypothalamus; Identification and classification; Infections; Inoculation; Iodide peroxidase; Iodide Peroxidase - genetics; Iodide Peroxidase - metabolism; Iodothyronine Deiodinase Type II; Kidneys; Missense mutation; Mutation; Mutation, Missense; Nonsynonymous mutation; Phenotypes; Pituitary; Polymorphism; Porcine reproductive and respiratory syndrome; Porcine Reproductive and Respiratory Syndrome - genetics; Porcine Reproductive and Respiratory Syndrome - virology; Porcine respiratory and reproductive syndrome virus - genetics; Pregnancy; PRRSV; Stress response; Survival; Swine; Thyroid; Thyroid gland; Thyroxine; Thyroxine deiodinase; Triiodothyronine; Viability
• ISSN: 1746-6148; 1746-6148
• DOI: 10.1186/s12917-024-04099-4

Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) infection during late gestation substantially lowers fetal viability and survival. In a previous genome-wide association study, a single nucleotide polymorphism on chromosome 7 was significantly associated with probability of fetuses being viable in response to maternal PRRSV-2 infection at 21 days post maternal inoculation. The iodothyronine deiodinase 2 (DIO2) gene, located ~ 14 Kilobase downstream of this SNP, was selected as a priority candidate related to fetal susceptibility following maternal PRRSV-2 infection. Our objectives were to identify mutation(s) within the porcine DIO2 gene and to determine if they were associated with fetal outcomes after PRRSV-2 challenge. Sequencing of the DIO2, genotyping identified variants, and association of DIO2 genotypes with fetal phenotypes including DIO2 mRNA levels, viability, survival, viral loads, cortisol and thyroid hormone levels, and growth measurements were conducted. A missense variant (p.Asn91Ser) was identified in the parental populations from two independent PRRSV-2 challenge trials. This variant was further genotyped to determine association with fetal PRRS outcomes. DIO2 mRNA levels in fetal heart and kidney differed by the genotypes of Asn91Ser substitution with significantly greater DIO2 mRNA expression in heterozygotes compared with wild-type homozygotes (P