Origin, evolution, and virulence of porcine deltacoronaviruses in the United States.
Origin, evolution, and virulence of porcine deltacoronaviruses in the United States.
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作者：
Ma Y;Zhang Y;Liang X;Lou F;Oglesbee M;Krakowka S;Li J
2014年2月在美国俄亥俄州和印第安纳州首次发现一种新型猪三角洲冠状病毒（PdCV），并迅速传播至美国其他州和加拿大，给养猪业造成重大经济损失。这种新型猪冠状病毒的起源和毒力尚不清楚。在这里，我们表征了美国PdCV分离株，并确定了它们在无菌仔猪和常规仔猪中的毒力。基因组分析显示，美国PdCV分离株具有独特的遗传特征，与香港和韩国PdCV株以及亚洲豹猫和中国雪貂的冠状病毒（CoV）有着密切的关系。将PdCV阳性肠内容物（俄亥俄州CVM 1）和细胞培养适应的PdCV密歇根（MI）菌株经口接种到无菌仔猪和/或常规仔猪中。感染后1至3天内，观察到大量水样腹泻、呕吐和脱水。临床体征与胃小凹和小肠上皮坏死相关，后者导致重度绒毛萎缩。在PdCV感染仔猪的肺中发现轻度间质性肺炎。在感染仔猪的肠组织/管腔内容物和粪便中检测到高水平的病毒RNA（8至11 log RNA拷贝/g），而在血液、肺、肝和肾中检测到中等水平的RNA（2至5 log RNA拷贝/g），表明病毒的多系统传播。抗PdCV多克隆免疫血清与PdCV感染的小肠上皮细胞发生反应，但不与猪流行性腹泻病毒（PEDV）免疫血清发生反应，表明PdCV与PEDV的抗原性不同。总的来说，我们首次证明PdCV在猪中引起严重的胃肠道疾病。猪冠状病毒（Porcine Coronaviruses，CoV）是猪的主要病毒性传染病。猪CoV的实例包括猪传染性胃肠炎冠状病毒（TGEV）、猪流行性腹泻病毒（PEDV）和猪呼吸道冠状病毒（PRCV）。2014年2月，另一种猪冠状病毒--猪三角洲冠状病毒（PdCV）在俄亥俄州和印第安纳州出现，随后在美国和加拿大迅速蔓延，造成重大经济损失。在这里，我们报告了详细的遗传特性，致病性和毒力的紧急PdCV株在美国。我们发现PdCV会导致非细菌性和传统小猪严重腹泻、呕吐和脱水，这些症状在临床上与PEDV和TGEV引起的症状难以区分。除了广泛的肠道病变外，PdCV还引起胃的显著病变和TGEV和PEDV尚未报道的轻度肺部病变。PdCV是一种重要的猪肠道疾病，这一发现强调了开发有效措施控制这种疾病的必要性。
A novel porcine deltacoronavirus (PdCV) was first discovered in Ohio and Indiana in February 2014, rapidly spread to other states in the United States and Canada, and caused significant economic loss in the swine industry. The origin and virulence of this novel porcine coronavirus are not known. Here, we characterized U.S. PdCV isolates and determined their virulence in gnotobiotic and conventional piglets. Genome analyses revealed that U.S. PdCV isolates possess unique genetic characteristics and share a close relationship with Hong Kong and South Korean PdCV strains and coronaviruses (CoVs) of Asian leopard cats and Chinese ferret-badgers. The PdCV-positive intestinal content (Ohio CVM1) and the cell culture-adapted PdCV Michigan (MI) strain were orally inoculated into gnotobiotic and/or conventional piglets. Within 1 to 3 days postinfection, profuse watery diarrhea, vomiting, and dehydration were observed. Clinical signs were associated with epithelial necrosis in the gastric pits and small intestine, the latter resulting in severe villous atrophy. Mild interstitial pneumonia was identified in the lungs of PdCV-infected piglets. High levels of viral RNA (8 to 11 log RNA copies/g) were detected in intestinal tissues/luminal contents and feces of infected piglets, whereas moderate RNA levels (2 to 5 log RNA copies/g) were detected in blood, lung, liver, and kidney, indicating multisystemic dissemination of the virus. Polyclonal immune serum against PdCV but not immune serum against porcine epidemic diarrhea virus (PEDV) reacted with PdCV-infected small-intestinal epithelial cells, indicating that PdCV is antigenically distinct from PEDV. Collectively, we demonstrate for the first time that PdCV caused severe gastrointestinal diseases in swine. Porcine coronaviruses (CoVs) are major viral infectious diseases of swine. Examples of porcine CoVs include porcine transmissible gastroenteritis coronavirus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine respiratory coronavirus (PRCV). In February 2014, another porcine CoV, porcine deltacoronavirus (PdCV), emerged in Ohio and Indiana and subsequently spread rapidly across the United States and Canada, causing significant economic losses. Here, we report the detailed genetic characterization, phylogeny, and virulence of emergent PdCV strains in the United States. We found that PdCV caused severe diarrhea, vomiting, and dehydration in gnotobiotic and conventional piglets, signs that were clinically indistinguishable from those caused by PEDV and TGEV. In addition to extensive intestinal lesions, PdCV caused significant lesions in the stomach and mild pulmonary lesions that have not been reported for TGEV and PEDV. The finding that PdCV is a significant enteric disease of swine highlights the need to develop effective measures to control this disease.