Meling Siv, Skovgaard Kerstin, Bårdsen Kjetil, Helweg Heegaard Peter Mikael, Ulvund Martha J
Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Sandnes, Norway.
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kemitorvet, 2800, Lyngby, Denmark.
BMC Vet Res. 2018 Sep 12;14(1):281. doi: 10.1186/s12917-018-1607-9.
Incubation period, disease progression, pathology and clinical presentation of classical scrapie in sheep are highly dependent on PRNP genotype, time and route of inoculation and prion strain. Our experimental model with pre-colostrum inoculation of homozygous VRQ lambs has shown to be an effective model with extensive PrP dissemination in lymphatic tissue and a short incubation period with severe clinical disease. Serum protein analysis has shown an elevation of acute phase proteins in the clinical stages of this experimental model, and here, we investigate changes in gene expression in whole blood, liver and brain.
The animals in the scrapie group showed severe signs of illness 22 weeks post inoculation necessitating euthanasia at 23 weeks post inoculation. This severe clinical presentation was accompanied by changes in expression of several genes. The following genes were differentially expressed in whole blood: TLR2, TLR4, C3, IL1B, LF and SAA, in liver tissue, the following genes differentially expressed: TNF-α, SAA, HP, CP, AAT, TTR and TF, and in the brain tissue, the following genes were differentially expressed: HP, CP, ALB and TTR.
We report a strong and evident transcriptional innate immune response in the terminal stage of classical scrapie in these animals. The PRNP genotype and time of inoculation are believed to contribute to the clinical presentation, including the extensive dissemination of PrP throughout the lymphatic tissue.
绵羊经典痒病的潜伏期、疾病进展、病理学及临床表现高度依赖于PRNP基因型、接种时间和途径以及朊病毒株。我们对纯合VRQ羔羊进行初乳前接种的实验模型已证明是一种有效的模型,其PrP在淋巴组织中广泛传播,潜伏期短且临床疾病严重。血清蛋白分析显示,在该实验模型的临床阶段急性期蛋白升高,在此,我们研究全血、肝脏和大脑中基因表达的变化。
痒病组动物在接种后22周出现严重疾病迹象,在接种后23周需要实施安乐死。这种严重的临床表现伴随着多个基因表达的变化。全血中差异表达的基因如下:TLR2、TLR4、C3、IL1B、LF和SAA;肝脏组织中差异表达的基因如下:TNF-α、SAA、HP、CP、AAT、TTR和TF;脑组织中差异表达的基因如下:HP、CP、ALB和TTR。
我们报道了这些动物在经典痒病末期存在强烈且明显的转录性固有免疫反应。PRNP基因型和接种时间被认为对临床表现有影响,包括PrP在整个淋巴组织中的广泛传播。