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.

中文翻译：

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恒河猴持续无症状埃博拉病毒感染的鉴定和病理学特征。

自2013-2016年西非爆发埃博拉病毒以来，无症状人类中的埃博拉病毒（EBOV）持续存在和埃博拉病毒病（EVD）后遗症已成为重要的公共卫生问题。到目前为止，由于缺乏合适的动物模型，研究EBOV如何在免疫弱势的部位传播和持续存在是不可能的。在这里，我们检测到持续的EBOV复制，与在无症状或没有候选药物对策的情况下在感染中幸存下来的无症状恒河猴的系统性炎症反应相吻合。我们记录了渐进性EBOV通过血管结构散布到眼睛，大脑和睾丸中，类似于在人类中的观察结果。我们识别出CD68 ⁺细胞（巨噬细胞/单核细胞）是玻璃体液及其紧邻组织中，附睾的管状腔中以及大脑中组织细胞炎症灶中的隐秘EBOV贮库细胞，但在通常在急性感染期间受影响的器官中没有。总之，我们的数据表明恒河猴持续性EBOV感染可以作为人类持续性EBOV感染的模型，并且我们证明，有希望的候选医学对策可能无法完全清除EBOV感染。恒河猴模型可能为研究EVD后遗症和开发消除EBOV持久性的疗法奠定基础。