Harding John C S, Ladinig Andrea, Novakovic Predrag, Detmer Susan E, Wilkinson Jamie M, Yang Tianfu, Lunney Joan K, Plastow Graham S
Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr., Saskatoon, Saskatchewan S7N 5B4, Canada.
Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
Vet Microbiol. 2017 Sep;209:114-123. doi: 10.1016/j.vetmic.2017.02.019. Epub 2017 Mar 2.
A large challenge experiment using North American porcine reproductive and respiratory virus (PRRSV-2) provided new insights into the pathophysiology of reproductive PRRS. Deep phenotyping of dams and fetuses identified maternal and fetal predictors of PRRS severity and resilience. PRRSV infection resulted in dramatic decreases in all leukocyte subsets by 2days post inoculation. Apoptosis in the interface region was positively related to endometrial vasculitis, viral load in endometrium and fetal thymus, and odds of meconium staining. Viral load at the maternal-fetal interface was a strong predictor of viral load in fetal thymus and odds of fetal death. However, interferon-alpha suppression, a consequence of PRRSV infection, was protective against fetal death. Although the prevalence of fetal lesions was low, their presence in fetal organs and umbilical cord was strongly associated with fetal compromise. Fetal death and viral load clustered in litters suggesting inter-fetal transmission starting from a limited number of index fetuses. Factors associated with index fetal infection are unclear, but large fetuses appear at greater risk. Disease progression in fetuses was associated with an up-regulation of genes associated with inflammation, innate immunity, and cell death signaling, and down-regulation of genes associated with cell cycle and lymphocyte quality. A number of maternal transcriptomic responses were associated with PRRS resilience including higher basal gene expression correlated with platelet function, interferon and pro-inflammatory responses. Twenty-one genomic regions across 10 chromosomes were associated with important traits including fetal viral load, fetal death and viability suggesting that selection for reproductive PRRS resilience may be possible.
一项使用北美猪繁殖与呼吸综合征病毒（PRRSV - 2）的大型挑战实验为繁殖型PRRS的病理生理学提供了新见解。对母猪和胎儿进行深度表型分析确定了PRRS严重程度和恢复力的母体及胎儿预测指标。接种后2天，PRRSV感染导致所有白细胞亚群显著减少。界面区域的细胞凋亡与子宫内膜血管炎、子宫内膜和胎儿胸腺中的病毒载量以及胎粪染色几率呈正相关。母胎界面处的病毒载量是胎儿胸腺中病毒载量和胎儿死亡几率的有力预测指标。然而，PRRSV感染导致的α干扰素抑制对胎儿死亡具有保护作用。尽管胎儿病变的发生率较低，但它们在胎儿器官和脐带中的存在与胎儿受损密切相关。胎儿死亡和病毒载量在窝内聚集，表明从有限数量的索引胎儿开始存在胎儿间传播。与索引胎儿感染相关的因素尚不清楚，但较大的胎儿似乎风险更高。胎儿疾病进展与炎症、先天免疫和细胞死亡信号相关基因的上调以及细胞周期和淋巴细胞质量相关基因的下调有关。许多母体转录组反应与PRRS恢复力相关，包括与血小板功能、干扰素和促炎反应相关的较高基础基因表达。10条染色体上的21个基因组区域与重要性状相关，包括胎儿病毒载量、胎儿死亡和活力，这表明有可能选择具有繁殖型PRRS恢复力的猪。
