Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) infection during late gestation negatively affects fetal development. The objective of this study was to identify the fetal organs most severely impacted following infection, and evaluate the relationship between this response and fetal phenotypes. RNA was extracted from fetal heart, liver, lung, thymus, kidney, spleen, and loin muscle, collected following late gestation viral challenge of pregnant gilts. Initially, gene expression for three cell cycle promoters (CDK1, CDK2, CDK4) and one inhibitor (CDKN1A) were evaluated in biologically extreme phenotypic subsets including gestational age-matched controls (CON), uninfected (UNIF), high-viral load viable (HV-VIA), and high-viral load meconium-stained (HV-MEC) fetuses. There were no differences between CON and UNIF groups for any gene, indicating no impact of maternal infection alone. Relative to CON, high-viral load (HV-VIA, HV-MEC) fetuses showed significant downregulation of at least one CDK gene in all tissues except liver, while CDKN1A was upregulated in all tissues except muscle, with the heart and kidney most severely impacted. Subsequent evaluation of additional genes known to be upregulated following activation of P53 or TGFb/SMAD signaling cascades indicated neither pathway was responsible for the observed increase in CDKN1A. Finally, analysis of heart and kidney from a larger unselected population of infected fetuses from the same animal study showed that serum thyroxin and viral load were highly correlated with the expression of CDKN1A in both tissues. Collectively these results demonstrate the widespread suppression in cell division across all tissues in PRRSV infected fetuses and indicate a non-canonical regulatory mechanism.
Highlights
Porcine reproductive and respiratory syndrome virus (PRRSV) initially emerged in the late 1980s and has since become one of the most economically devastating pathogens affecting swine production
Expression of cell cycle promoters across seven fetal organs To understand the impact of fetal PRRSV infection on late gestation organ development, we evaluated expression of three cell cycle promoters (CDK1, 2, and 4) and the suppressor cyclic dependent kinase inhibitor 1A (CDKN1A) across seven fetal tissues derived from established fetal phenotypes
In SPLN, a significant decrease in expression of CDK1 was observed in both high-viral load viable (HV-VIA) (x = −1.58 fold, P = 0.076) and high-viral load meconium-stained (HV-more severe face and body (MEC)) (x = −2.16 fold, P = 0.076) fetuses relative to CON
Summary
Porcine reproductive and respiratory syndrome virus (PRRSV) initially emerged in the late 1980s and has since become one of the most economically devastating pathogens affecting swine production. The virus exhibits an exceptionally high mutation rate, with roughly one mutation expected per viral replication cycle [2], resulting in an ongoing re-emergence of novel strains. PRRSV is of particular concern within the breeding herd, where it can lead to abortion and a significant increase in the number of stillborn and weak piglets in pregnancies carried to term. These negative reproductive outcomes arise following vertical
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
