Pathogenesis of experimental Ebola Zaire virus infection in BALB/c mice
Pathogenesis of experimental Ebola Zaire virus infection in BALB/c mice
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DOI：
10.1053/jcpa.2001.0502
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发表时间：
2001-11-01
影响因子：
0.8
通讯作者：
Jaax, NK
中科院分区：
文献类型：
--
作者：
Gibb, TR;Bray, M;Jaax, NK
传统上，豚鼠和非人类灵长类动物被用作研究埃博拉扎伊尔病毒感染的动物模型。该病毒最近也适应了BALB/c小鼠的致死毒力阶段。这种小鼠模型现在被用于测试抗病毒药物和疫苗。然而，小鼠感染EBO-Z的病理特征尚未完全描述。为了确定病毒复制位点并表征BALB/c小鼠的序列形态学变化，将成年雌性小鼠感染小鼠适应型EBO-Z，并在感染后5天内各组杀死。采用光镜、免疫组化、电镜、原位杂交等方法检查组织。与豚鼠和非人类灵长类动物一样，单核吞噬系统的细胞是感染的最早目标。第2天观察到病毒在淋巴结和脾脏巨噬细胞中的复制。到发病和体重减轻时（第3天），感染已经扩散到肝细胞和肾上腺皮质细胞，以及许多器官中的巨噬细胞和成纤维细胞样细胞。脾脏、淋巴结及胸腺均见严重淋巴细胞溶解。内皮细胞感染极少。所有这些变化与ebo - z感染豚鼠和非人灵长类动物中观察到的变化相似。然而，与其他动物模型相比，在疾病晚期有憎恨纤维蛋白沉积。免疫缺陷、“基因敲除”和转基因小鼠的可用性将使小鼠模型对研究埃博拉发病机制的主要步骤特别有用。
Guinea-pigs and non-human primates have traditionally been used as animal models for studying Ebola Zaire virus (EBO-Z) infections. The virus was also recently adapted to the stage of lethal virulence in BALB/c mice. This murine model is now in use for testing antiviral medications :and vaccines. However, the pathological features of EBO-Z infection in mice have not yet been fully described. To identify sites of viral replication and characterize sequential morphological changes in BALB/c mice, adult female mice were infected with mouse-adapted EBO-Z and killed in groups each da, for 5 da ls post-infection. Tissues were examined by light microscopy, immunohistochemistry, electron microscope, and in-situ hybridization. As in guinea-pigs and non-human primates, cells of the mononuclear phagocytic system were the earliest targets of infection. Viral replication was observed by day 2 in macrophages in lymph nodes and spleen. By the time of onset of illness and weight loss (day 3), the Infection had spread to hepatocytes and adrenal cortical cells, and to macrophages and fibroblast-like cells in many, organs. Severe lymphocytolysis was observed in the spleen, lymph nodes and thymus. There was minimal infection of endothelial cells. All of these changes resembled those observed in EBO-Z-infected guinea-pigs and non-human primates. In contrast to the other animal models, however, there was Hate fibrin deposition in the late stage of disease. The availability of immunodeficient, "gene-knockout" and transgenic mice will make the mouse model particularly, useful for studying the earls, steps of Ebola pathogenesis.