Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus.
Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus.
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DOI：
10.1016/s0002-9440(10)62989-6
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发表时间：
2005-08
影响因子：
6
通讯作者：
Mansfield, K
中科院分区：
文献类型：
--
作者：
Greenough, TC;Carville, A;Coderre, J;Somasundaran, M;Sullivan, JL;Luzuriaga, K;Mansfield, K
严重急性呼吸综合征（SARS）是一种重要的新发传染病。感染病原体SARS相关冠状病毒（SARS-CoV）的人主要表现为肺炎，但也可能出现肝脏、胃肠道和肾脏病理。我们接种普通绒猴（Callithrix jacchus），目的是建立一个小型非人灵长类动物SARS模型。两组C.用含有SARS-CoV的细胞培养上清液进行肠内接种。在一项时程发病机制研究中，在感染后2、4和7天评价动物的形态学变化和病毒复制的证据。所有动物均发生多灶性单核细胞间质性肺炎，大多数动物伴有多核合胞体细胞、水肿和细支气管炎。免疫组化显示，病毒抗原主要定位于感染的肺泡巨噬细胞和1型肺细胞。在尸检时获得的肺组织提取物中，在所有动物中均检出病毒RNA。在部分动物的气管支气管淋巴结和心肌中也检测到病毒RNA，并伴有炎症变化。在大多数动物中观察到肝脏炎症，主要表现为多灶性淋巴细胞性肝炎，伴有单个肝细胞坏死。这些发现确定普通绒猴作为一个有前途的非人灵长类动物研究SARS冠状病毒的发病机制。
Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis.