Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
J Infect Dis. 2020 Oct 13;222(10):1745-1755. doi: 10.1093/infdis/jiaa304.
Neurological signs and symptoms are the most common complications of Ebola virus disease. However, the mechanisms underlying the neurologic manifestations in Ebola patients are not known. In this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to Ebola virus (EBOV) disease from 5 to 8 days post exposure. Ganglionitis, characterized by neuronal degeneration, necrosis, and mononuclear leukocyte infiltrates, was observed in the dorsal root, autonomic, and enteric ganglia. By immunohistochemistry, RNAscope in situ hybridization, transmission electron microscopy, and confocal microscopy, we confirmed that CD68+ macrophages are the target cells for EBOV in affected ganglia. Further, we demonstrated that EBOV can induce satellite cell and neuronal apoptosis and microglial activation in infected ganglia. Our results demonstrate that EBOV can infect peripheral ganglia and results in ganglionopathy in rhesus macaques, which may contribute to the neurological signs and symptoms observed in acute and convalescent Ebola virus disease in human patients.
神经系统症状和体征是埃博拉病毒病最常见的并发症。然而，埃博拉患者神经系统表现的机制尚不清楚。在这项研究中，从感染后 5 至 8 天死于埃博拉病毒（EBOV）病的 12 只恒河猴中收集外周神经节。在背根、自主和肠神经节中观察到以神经元变性、坏死和单核白细胞浸润为特征的神经节炎。通过免疫组织化学、RNAscope 原位杂交、透射电子显微镜和共聚焦显微镜，我们证实 CD68+巨噬细胞是受感染神经节中 EBOV 的靶细胞。此外，我们证明 EBOV 可诱导感染神经节中的卫星细胞和神经元凋亡以及小胶质细胞激活。我们的研究结果表明，EBOV 可感染外周神经节，并导致猕猴发生神经节病，这可能导致人类急性和恢复期埃博拉病毒病中观察到的神经系统症状和体征。
