Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Fort Detrick, Frederick, MD, 21702, USA.
Emory Eye Center, Emory University, Atlanta, GA, 30322, USA.
Commun Biol. 2022 Nov 9;5(1):1204. doi: 10.1038/s42003-022-04158-2.
Despite increasing evidence that uveitis is common and consequential in survivors of Ebola virus disease (EVD), the host-pathogen determinants of the clinical phenotype are undefined, including the pathogenetic role of persistent viral antigen, ocular tissue-specific immune responses, and histopathologic characterization. Absent sampling of human intraocular fluids and tissues, these questions might be investigated in animal models of disease; however, challenges intrinsic to the nonhuman primate model and the animal biosafety level 4 setting have historically limited inquiry. In a rhesus monkey survivor of experimental Ebola virus (EBOV) infection, we observed and documented the clinical, virologic, immunologic, and histopathologic features of severe uveitis. Here we show the clinical natural history, resultant ocular pathology, intraocular antigen-specific antibody detection, and persistent intraocular EBOV RNA detected long after clinical resolution. The association of persistent EBOV RNA as a potential driver of severe immunopathology has pathophysiologic implications for understanding, preventing, and mitigating vision-threatening uveitis in EVD survivors.
尽管越来越多的证据表明,埃博拉病毒病(EVD)幸存者中普遍存在葡萄膜炎且后果严重,但临床表型的宿主-病原体决定因素尚不清楚,包括持续病毒抗原、眼部组织特异性免疫反应和组织病理学特征的致病作用。由于无法采集人类眼内液和组织样本,这些问题可能需要在疾病的动物模型中进行研究;然而,由于非人类灵长类动物模型和动物生物安全 4 级环境固有的挑战,历史上限制了相关研究。在一名感染埃博拉病毒(EBOV)的实验性猕猴幸存者中,我们观察并记录了严重葡萄膜炎的临床、病毒学、免疫学和组织病理学特征。在此,我们展示了临床自然病史、眼部病理学结果、眼内抗原特异性抗体检测以及在临床缓解后很长时间内持续存在的眼内 EBOV RNA。持续存在的 EBOV RNA 作为严重免疫病理的潜在驱动因素,这对理解、预防和减轻 EVD 幸存者的致盲性葡萄膜炎具有病理生理学意义。