Gene expression in heart, kidney, and liver identifies possible mechanisms underpinning fetal resistance and susceptibility to in utero PRRSV infection

• Published in: Veterinary microbiology Vol. 295; p. 110154
• Main Authors: Walker, K.E., Pasternak, J.A., Jones, A., Mulligan, M.K., Van Goor, A., Harding, J.C.S., Lunney, J.K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2024
• Subjects: Aldosterone; Chemotaxis; Energy; Fetal compromise; Gene expression; Pig disease; PRRSV; Transporters; Virus transmission; Virus-host interaction; Virus transmission; Energy; Transporters; Virus-host interaction; Aldosterone; Gene expression; Chemotaxis; PRRSV; Pig disease; Fetal compromise
• ISSN: 0378-1135; 1873-2542; 1873-2542
• DOI: 10.1016/j.vetmic.2024.110154

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. [Display omitted] •Fetal response to late gestation PRRSV infection is dependent on viral load and preservation status.•Infection alters gene expression associated with blood pressure, glucose transport, sodium homeostasis and immune response.•Gene expression changes associated with fetal susceptibility were prominent in fetal liver, followed by kidney and heart.