Fetal cytokine response to porcine reproductive and respiratory syndrome virus-2 infection

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2020-02, Vol.126, p.154883-154883, Article 154883
• Main Authors: Alex Pasternak, J., MacPhee, Daniel J., Harding, John C.S.
• Format: Article
• Language: English
• Subjects: Cell cycle; Fetus; Host-virus interaction; Interferon; Porcine; PRRSV; Resilience
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2019.154883

•Fetal immune response during maternal PRRSV infection is largely restricted to infected fetuses.•Over expression of CCL5 is associated with disease progression and reduced fetal viability.•Differences were found between gene expression and abundance of type 1, but not type 2, interferons.•Regulation of cell cycle progression is significantly altered in highly PRRSV-infected tissue. To understand the fetal immune response to porcine reproductive and respiratory virus-2 (PRRSV) and to evaluate the association with fetal viability, pregnant gilts were challenged on gestation day 85 and euthanized 21 days post infection. Based on preservation status and viral load in serum and thymus, fetuses were classified as either uninfected-viable (UNIF), high viral load viable (HV-VIA), or high viral load meconium stained (HV-MEC) and were compared with age matched control (CON) fetuses derived from mock infected gilts. Gene expression of IFNB, IFNG, CCL2, CCL5, CXCL10 and IL10, were all found to be significantly upregulated in the thymus and spleen of both high viral load groups. UNIF fetuses remained largely unaffected, with only small upregulations in IFNA and IL10 in the thymus, and IFNA, CCL5 and CXCL10 in the spleen. Regarding fetal viability, expression of CCL5 was significantly elevated in the thymus and spleen of HV-MEC compared to HV-VIA fetuses. The concentrations of IFNα, IFNγ, TNFα and CCL2 were elevated in the sera of all infected fetuses, whereas IFNβ was below the detection limit in all fetal sera. Additional gene expression analysis in the thymus showed significant downregulation of CDK1, CDK2 and CDK4, and upregulation of the inhibitor CDKN1A, suggesting altered regulation of cell cycle progression. Collectively, these results show near complete compartmentalization of the fetal immune response to infected fetuses and suggest this immune response is not a major contributor to fetal death.