Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment.
Ebola Virus Replication and Disease Without Immunopathology in Mice Expressing Transgenes to Support Human Myeloid and Lymphoid Cell Engraftment.
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表达转基因支持人骨髓和淋巴细胞移植的小鼠中埃博拉病毒复制和疾病无需免疫病理学。
DOI：
10.1093/infdis/jiw248
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Prescott,Joseph
中科院分区：
文献类型：
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作者：
Spengler,JessicaR;Lavender,KerryJ;Martellaro,Cynthia;Carmody,Aaron;Kurth,Andreas;Keck,JamesG;Saturday,Greg;Scott,DanaP;Nichol,StuartT;Hasenkrug,KimJ;Spiropoulou,ChristinaF;Feldmann,Heinz;Prescott,Joseph
埃博拉病毒（EBOV）体内发病机制的研究仅限于非人类灵长类动物模型或使用适应的病毒在啮齿类动物模型中引起疾病。在此，我们描述了植入人类造血 CD34+ 干细胞的小鼠（Hu-NSG™-SGM3 小鼠；以下称为 SGM3 HuMice）的野生型 EBOV（Makona 变种）感染。 SGM3 HuMice 支持促进骨髓免疫细胞的发育，这是 EBOV 的主要目标。在 SGM3 HuMice 中，埃博拉病毒复制到高水平，并且在腹膜内或肌肉内接种后观察到疾病。尽管肝脏中存在高水平的病毒抗原和炎症细胞浸润，但没有观察到埃博拉病毒病的特征性组织病理学，并且这种严重免疫病理学的缺乏可能有助于一些动物的恢复和生存。未来对 SGM3 HuMice 中非典型疾病表现的潜在机制的研究将为严重 EBOV 疾病的免疫发病机制提供更多见解。
The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34+stem cells (Hu-NSG™-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation. Despite the high levels of viral antigen and inflammatory cell infiltration in the liver, the characteristic histopathology of Ebola virus disease was not observed, and this absence of severe immunopathology may have contributed to the recovery and survival of some of the animals. Future investigations into the underlying mechanisms of the atypical disease presentation in SGM3 HuMice will provide additional insights into the immunopathogenesis of severe EBOV disease.