Understanding fetal immune responses to congenital porcine reproductive and respiratory syndrome virus infection

Abstract

Abstract Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most economically significant diseases in the global swine industry, causing late-term abortions, early farrowing, and respiratory disease. Few studies have previously explored the immune pathways that alter fetal PRRS resistance/ susceptibility. Using a model where 3rd trimester pregnant gilts were euthanized at 2, 5, 8, 12, or 14 days post infection (DPI) with PRRS virus (PRRSV), samples from the fetal thymus and placenta, and maternal endometrium were collected and viral loads measured (U Saskatchewan) to determine when the virus crosses the placental barrier and infects each fetus. RNA was extracted with a Qiagen RNA Isolation kit, and gene expression determined using a 220 gene NanoString array to evaluate differential expression (DE) of genes and biomarkers previously predicted to alter PRRS resistance and susceptibility. Selected biomarkers that were measured included interferon signaling pathways, TREM1, HMGB1, B and T cell receptors, cell division, apoptosis, tissue remodeling and epithelial integrity, based on pathways identified using Ingenuity Pathway Analysis. Fetuses from the control gilt will be compared to those from three PRRSV infected gilts from the same DPI based on serum and thymus viral levels, comparing their viral negative (uninfected) and viral positive (infected) fetuses from the same litter. Comparisons of DE genes will be made between neighboring fetuses and across DPI. Data should reveal immunological pathways that contribute to fetal susceptibility. Understanding these mechanisms will benefit future research dedicated to exploring targeted approaches to halt the congenital spread of this disease.