Arruda Bailey L, Arruda Paulo H, Magstadt Drew R, Schwartz Kent J, Dohlman Tyler, Schleining Jennifer A, Patterson Abby R, Visek Callie A, Victoria Joseph G
Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.
Boehringer Ingelheim Vetmedica, Inc., Ames, Iowa, United States of America.
PLoS One. 2016 Feb 24;11(2):e0150104. doi: 10.1371/journal.pone.0150104. eCollection 2016.
Congenital tremors is a sporadic disease of neonatal pigs characterized by action-related repetitive myoclonus. A majority of outbreaks of congenital tremors have been attributed to an unidentified virus. The objectives of this project were to 1) detect potential pathogen(s) in samples from piglets with congenital tremors and 2) develop an infection model to reproduce disease. Using next-generation sequencing, a divergent lineage pestivirus was detected in piglets with congenital tremors. The virus was originally most closely related to a bat pestivirus but is now more closely related to a recently published novel porcine pestivirus provisionally named atypical porcine pestivirus. A quantitative real-time PCR detected the virus in samples from neonatal piglets with congenital tremors from two separate farms, but not in samples from unaffected piglets from the same farm. To fulfill the second objective, pregnant sows were inoculated with either serum containing the pestivirus or PBS (control) by intravenous and intranasal routes simultaneously with direct inoculation of fetal amniotic vesicles by ultrasound-guided surgical technique. Inoculations were performed at either 45 or 62 days of gestation. All sows inoculated with the novel pestivirus farrowed piglets affected with congenital tremors while PBS-inoculated control piglets were unaffected. Tremor severity for each piglet was scored from videos taken 0, 1 and 2 days post-farrowing. Tremor severity remained relatively constant from 0 to 2 days post-farrowing for a majority of piglets. The prevalence of congenital tremors in pestivirus-inoculated litters ranged from 57% (4 out of 7 affected piglets) to 100% (10 out of 10 affected piglets). The virus was consistently detected by PCR in tissues from piglets with congenital tremors but was not detected in control piglets. Samples positive by PCR in greater than 90% of piglets sampled included brainstem (37 out of 41), mesenteric lymph node (37 out of 41), tracheobronchial lymph node (37 out of 41), and whole blood (19 out of 20). Although the first description of congenital tremors was in 1922, this is the first reported reproduction of congenital tremors following experimental inoculation with a divergent lineage porcine pestivirus. Studies investigating disease mechanism, epidemiology, and diagnostic assay development are needed to better understand the pathophysiology of congenital tremors due to this pestivirus.
先天性震颤是新生仔猪的一种散发性疾病，其特征为与动作相关的重复性肌阵挛。大多数先天性震颤疫情都归因于一种不明病毒。本项目的目标是：1）检测先天性震颤仔猪样本中的潜在病原体；2）建立一种感染模型以再现该疾病。通过下一代测序，在先天性震颤仔猪中检测到一种不同谱系的瘟病毒。该病毒最初与一种蝙蝠瘟病毒关系最为密切，但现在与最近公布的一种新的猪瘟病毒（暂命名为非典型猪瘟病毒）关系更为密切。定量实时PCR在来自两个不同农场的先天性震颤新生仔猪样本中检测到了该病毒，但在同一农场未受影响的仔猪样本中未检测到。为实现第二个目标，对怀孕母猪通过静脉内和鼻内途径同时接种含有瘟病毒的血清或PBS（对照），并通过超声引导手术技术直接接种胎儿羊膜囊。在妊娠45天或62天时进行接种。所有接种新型瘟病毒的母猪所产仔猪均患有先天性震颤，而接种PBS的对照仔猪未受影响。从分娩后0、1和2天拍摄的视频中对每头仔猪的震颤严重程度进行评分。大多数仔猪在分娩后0至2天震颤严重程度保持相对稳定。接种瘟病毒的仔猪窝中先天性震颤的患病率在57%（7头受影响仔猪中的4头）至100%（10头受影响仔猪中的10头）之间。通过PCR在患有先天性震颤的仔猪组织中始终检测到该病毒，但在对照仔猪中未检测到。在超过90%的采样仔猪中PCR呈阳性的样本包括脑干（41个中的37个）、肠系膜淋巴结（41个中的37个）、气管支气管淋巴结（41个中的37个）和全血（20个中的19个）。尽管先天性震颤的首次描述是在1922年，但这是首次报道在用不同谱系的猪瘟病毒进行实验接种后再现先天性震颤。需要开展研究以调查疾病机制、流行病学和诊断检测方法的开发，以便更好地了解由这种瘟病毒引起的先天性震颤的病理生理学。
