Complex immunogenomic control of serum thyroid hormone levels in fetuses and piglets challenged with Porcine Reproductive and Respiratory Syndrome Virus

Abstract

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) causes respiratory disease in piglets and reproductive disease in sows. However, the interaction between host immunity and hormone homeostasis is not completely understood but piglet and fetal serum thyroid hormone (i.e., T3 and T4) levels decrease rapidly in response to PRRSV infection. Our objective was to estimate genetic parameters, identify QTL, and uncover nearby candidate genes for T3 and/or T4 levels of piglets and fetuses challenged with PRRSV2. Serum from 5-week old pigs (N=1792) at 11 days post infection (dpi) with PRRSV2 were assayed for T3 levels (piglet_T3). While serum from fetuses (N=1267) at 12 or 21 dpi from sows (N=150) challenged with PRRSV2 in late gestation were assayed for T3 (fetal_T3) and T4 (fetal_T4) levels. Animals were genotyped for 60K or 650K SNPs, heritabilities were estimated and genome wide association studies were performed for each trait separately. We found all three traits to be moderately heritable (18–28%) and the significant QTL (N=37) across several chromosomes collectively explained 24–34% of the genetic variation. A shared QTL identified for all traits on chromosome 6 contained the IL12RB2 and IFI44 genes. The largest QTL identified for both piglet_T3 and fetal_T3 on chromosome 5 contained IL17RA. A large QTL identified for piglet_T3 on chromosome 7 contained 9 MHC genes (e.g., SLA-DMA, SLA-DOA, SLA-DQA, SLA-DRA, and MHC-IA7). In conclusion, our data support the concept that there are complex interactions between thyroid hormone levels and multiple immunogenetic pathways during PRRSV infection, and that there is potential to select for pleiotropic QTL to simultaneously improve host immunity for reproductive and respiratory PRRS.