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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.<\/jats:p>","DOI":"10.1186\/s13567-022-01030-3","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:10:51Z","timestamp":1645467051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Porcine reproductive and respiratory virus 2 infection of the fetus results in multi-organ cell cycle suppression"],"prefix":"10.1186","volume":"53","author":[{"given":"Margaret K.","family":"Mulligan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn E.","family":"Kleiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Caldemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C. 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