To better understand the host response to porcine reproductive and respiratory virus-2 (PRRSV2) we evaluated circulating thyroid hormone and associated gene expression in a late gestation challenge model. Pregnant gilts were inoculated at gestation day 85 and fetal samples collected at either 12 or 21 days post-infection (dpi). A subset of fetuses was selected for analysis based on viability and viral load categorized as either uninfected-viable (UNIF), high viral load viable (HV-VIA) or high viral load meconium stained (HV-MEC) and were compared with gestational age matched controls (CON). In dams, circulating levels of total T3 and T4 decreased in the acute period following infection and rebounded by 21 dpi. A similar effect was observed in fetuses, but was largely restricted to HV-VIA and HV-MEC, with minimal decrease noted in UNIF relative to CON at 21 dpi. Gene expression in fetal heart at 12 dpi showed significant decompensatory transcription of thyroid hormone transporters (SLC16A2) and deiodinases (DIO2, DIO3), which was not observed in brain. Correspondingly, genes associated with cell cycle progression (CDK1,2,4) were downregulated in only the heart of highly infected fetuses, while expression of their inhibitor (CDKN1A) was upregulated in both tissues. Finally, expression of genes associated with cardiac stress including CAMKD and AGT were upregulated in the hearts of highly infected fetuses, and a shift in expression of MYH6 to MYH7 was observed in HV-MEC fetuses specifically. Collectively, the results suggest PRRSV2 infection causes a hypothyroid state that disproportionally impacts the fetal heart over the brain.

中文翻译：

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猪繁殖与呼吸综合征病毒2感染后的母婴甲状腺功能障碍

为了更好地了解宿主对猪生殖和呼吸道病毒2（PRRSV2）的反应，我们在晚期妊娠激发模型中评估了循环甲状腺激素和相关基因的表达。在妊娠第85天接种小母猪，并在感染后（dpi）12或21天收集胎儿样品。根据存活率和病毒载量选择胎儿的一个子集进行分析，病毒载量分为未感染活菌（UNIF），高病毒载菌（HV-VIA）或高病毒载量胎粪染（HV-MEC），并与胎龄进行比较匹配的控件（CON）。在大坝中，感染后的急性期总T3和T4的循环水平下降，并反弹21 dpi。在胎儿中也观察到类似的效果，但主要限于HV-VIA和HV-MEC，与21 dpi时的CON相比，UNIF的下降幅度最小。胎儿心脏在12 dpi时的基因表达表明甲状腺激素转运蛋白（SLC16A2）和脱碘酶（DIO2，DIO3）明显失代偿转录，而在大脑中未观察到。相应地，与细胞周期进程相关的基因（CDK1,2,4）仅在高度感染的胎儿心脏中被下调，而其抑制剂（CDKN1A）的表达在两个组织中均被上调。最后，在高度感染的胎儿的心脏中与心脏应激相关的基因（包括CAMKD和AGT）的表达上调，并且在HV-MEC胎儿中特别观察到MYH6向MYH7表达的转变。总体而言，这些结果表明PRRSV2感染会导致甲状腺功能减退，从而过度影响大脑上方的胎儿心脏。胎儿心脏在12 dpi时的基因表达表明甲状腺激素转运蛋白（SLC16A2）和脱碘酶（DIO2，DIO3）明显失代偿转录，而在大脑中未观察到。相应地，与细胞周期进程相关的基因（CDK1,2,4）仅在高度感染的胎儿心脏中被下调，而其抑制剂（CDKN1A）的表达在两个组织中均被上调。最后，在高度感染的胎儿的心脏中与心脏应激相关的基因（包括CAMKD和AGT）的表达上调，并且在HV-MEC胎儿中特别观察到MYH6向MYH7表达的转变。总体而言，这些结果表明PRRSV2感染会导致甲状腺功能减退，从而过度影响大脑上方的胎儿心脏。胎儿心脏在12 dpi时的基因表达表明甲状腺激素转运蛋白（SLC16A2）和脱碘酶（DIO2，DIO3）明显失代偿转录，而在大脑中未观察到。相应地，与细胞周期进程相关的基因（CDK1,2,4）仅在高度感染的胎儿心脏中被下调，而其抑制剂（CDKN1A）的表达在两个组织中均被上调。最后，在高度感染的胎儿的心脏中与心脏应激相关的基因（包括CAMKD和AGT）的表达上调，并且在HV-MEC胎儿中特别观察到MYH6向MYH7的表达变化。总体而言，这些结果表明PRRSV2感染会导致甲状腺功能减退，从而过度影响大脑上方的胎儿心脏。