Identification and pathological characterization of persistent asymptomatic Ebola virus infection in rhesus monkeys
Identification and pathological characterization of persistent asymptomatic Ebola virus infection in rhesus monkeys
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DOI：
10.1038/nmicrobiol.2017.113
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发表时间：
2017-09-01
影响因子：
28.3
通讯作者：
Sun, Mei G.
中科院分区：
文献类型：
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作者：
Zeng, Xiankun;Blancett, Candace D.;Sun, Mei G.
自2013-2016年西非埃博拉病毒暴发以来，埃博拉病毒在无症状人群中的持续存在和埃博拉病毒病（EVD）后遗症已成为重大公共卫生问题。到目前为止，由于缺乏合适的动物模型，研究EBOV如何传播到免疫特权部位并持续存在是不可能的。在本研究中，我们检测到持续的EBOV复制与系统性炎症反应相吻合，这些无症状的恒河猴在没有或经过候选医疗对策治疗的情况下存活下来。我们记录了EBOV通过血管结构逐渐传播到眼睛、大脑和睾丸，与人类的观察结果相似。我们发现CD68（+）细胞（巨噬细胞/单核细胞）是EBOV的隐库细胞，存在于玻璃体及其邻近组织、附睾管状腔和脑组织细胞炎症灶中，但不存在于急性感染时典型受影响的器官中。总之，我们的数据表明恒河猴的持续EBOV感染可以作为人类持续EBOV感染的模型，我们证明了有希望的候选医疗对策可能无法完全清除EBOV感染。恒河猴模型可以为研究埃博拉病毒后遗症和开发消除埃博拉病毒持久性的治疗方法奠定基础。
Ebola virus (EBOV) persistence in asymptomatic humans and Ebola virus disease (EVD) sequelae have emerged as significant public health concerns since the 2013-2016 EVD outbreak in Western Africa. Until now, studying how EBOV disseminates into and persists in immune-privileged sites was impossible due to the absence of a suitable animal model. Here, we detect persistent EBOV replication coinciding with systematic inflammatory responses in otherwise asymptomatic rhesus monkeys that had survived infection in the absence of or after treatment with candidate medical countermeasures. We document progressive EBOV dissemination into the eyes, brain and testes through vascular structures, similar to observations in humans. We identify CD68(+) cells (macrophages/monocytes) as the cryptic EBOV reservoir cells in the vitreous humour and its immediately adjacent tissue, in the tubular lumina of the epididymides, and in foci of histiocytic inflammation in the brain, but not in organs typically affected during acute infection. In conclusion, our data suggest that persistent EBOV infection in rhesus monkeys could serve as a model for persistent EBOV infection in humans, and we demonstrate that promising candidate medical countermeasures may not completely clear EBOV infection. A rhesus monkey model may lay the foundation to study EVD sequelae and to develop therapies to abolish EBOV persistence.