Gene expression in heart, kidney, and liver identifies mechanisms involved in fetal resilience to congenital PRRSV infection

Authors: Walker, Kristen; PASTERNAK, J ALEX - Purdue University; JONES, ADRIAN - St George'S University; MULLIGAN, MARGARET K - Purdue University; Van Goor, Angelica; HARDING, JOHN C S - University Of Saskatchewan; Lunney, Joan

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/12/2024
Publication Date: 7/2/2024
Citation: Walker, K.E., Pasternak, J., Jones, A., Mulligan, M., Van Goor, A.G., Harding, J., Lunney, J.K. 2024. Gene expression in heart, kidney, and liver identifies mechanisms involved in fetal resilience to congenital PRRSV infection. Veterinary Microbiology. 295(1): Article e110154. https://doi.org/10.1016/j.vetmic.2024.110154.
DOI: https://doi.org/10.1016/j.vetmic.2024.110154

Interpretive Summary: Our research focuses on understanding the fetal pig’s response to congenital porcine reproductive and respiratory syndrome virus (PRRSV) infection. We aimed to identify critical genes and tissues affecting viable, resilient fetuses, those with high viral load but projected to survive PRRS, versus PRRS susceptible fetuses, those with high viral load but covered with meconium aspiration. We observed differential gene expression varying by tissue in susceptible as compared to resilient fetuses: an increase in CCL5 for heart and kidney indicating effects on immune responses, and a decrease in ACE2 in kidney possibly affecting blood pressure regulation. Fetal liver had unique gene expression with increases in AGTR1 suggesting possible effects on blood pressure regulation, in KL implying tissue specific responses, in SLC16A1, SLC16A7, SLC27A1 which may be altering energy conversion mechanisms, and in TGFB affecting growth modulation. Increases in IL10, and a decrease in CXCL10, suggested effects on liver immune response. These results shed light on mechanisms of fetal protection against maternal PRRSV infection, the costliest disease for pork producers.

Technical Abstract: Porcine reproductive and respiratory syndrome (PRRS) is one of the costliest diseases to pork producers worldwide. We tested samples from the pregnant gilt model (PGM) to better understand the fetal response to in-utero PRRS virus (PRRSV) infection. Our goal was to identify critical tissues and genes associated with fetal resilience or susceptibility. Pregnant gilts (N=22) were infected with PRRSV on day 86 of gestation. At 21 days post maternal infection, the gilts and fetuses were euthanized, and fetal tissues collected. Fetuses were characterized for PRRS viral load in fetal serum and thymus, and preservation status (viable or meconium stained: VIA or MEC). Fetuses (N=10 per group) were compared: uninfected (UNIF; <1'log/µL PRRSV RNA), resilient (HV_VIA, >5'log virus/µL but viable), and susceptible (HV_MEC, >5'log virus/µL with MEC). Gene expression in fetal heart, kidney, and liver was investigated using NanoString transcriptomics. Gene categories investigated were hypothesized to be involved in fetal response to PRRSV infection: renin- angiotensin-aldosterone, inflammatory, transporter and metabolic systems. Following PRRSV infection, CCL5 increased expression in heart and kidney, and ACE2 decreased expression in kidney, each associated with fetal PRRS susceptibility. Liver revealed the most significant differential gene expression: CXCL10 decreased and IL10 increased indicative of immune suppression. Increased liver gene expression indicated potential associations with fetal PRRS susceptibility on several systems including blood pressure regulation (AGTR1), energy metabolism (SLC16A1 and SLC16A7), tissue specific responses (KL) and growth modulation (TGFB1). Overall, analyses of non-lymphoid tissues provided clues to mechanisms of fetal compromise following maternal PRRSV infection.