Communications Biology ( IF 5.2 ) Pub Date : 2022-11-09 , DOI: 10.1038/s42003-022-04158-2 Gabriella Worwa 1 , Timothy K Cooper 1 , Steven Yeh 2, 3 , Jessica G Shantha 2 , Amanda M W Hischak 1 , Sarah E Klim 1 , Russell Byrum 1 , Jonathan R Kurtz 1 , Scott M Anthony 1 , Nina M Aiosa 1 , Danny Ragland 1 , Ji Hyun Lee 1 , Marisa St Claire 1 , Carl Davis 4 , Rafi Ahmed 4 , Michael R Holbrook 1 , Jens H Kuhn 1 , Erica Ollmann Saphire 5 , Ian Crozier 1, 6
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.
中文翻译:
持续性眼内埃博拉病毒 RNA 与恢复期恒河猴的严重葡萄膜炎有关
尽管越来越多的证据表明葡萄膜炎在埃博拉病毒病(EVD)幸存者中很常见且后果严重,但临床表型的宿主病原体决定因素尚不清楚,包括持久性病毒抗原的致病作用、眼组织特异性免疫反应和组织病理学特征。如果没有对人类眼内液和组织进行取样,这些问题可能会在疾病动物模型中进行研究;然而,非人类灵长类动物模型和动物生物安全 4 级设置所固有的挑战历来限制了研究。在实验性埃博拉病毒(EBOV)感染的恒河猴幸存者中,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。在这里,我们展示了临床自然史、由此产生的眼部病理学、眼内抗原特异性抗体检测以及临床缓解后长时间检测到的持续眼内 EBOV RNA。持久性 EBOV RNA 作为严重免疫病理学潜在驱动因素的关联对于理解、预防和减轻埃博拉病毒病幸存者威胁视力的葡萄膜炎具有病理生理学意义。