Persistent intraocular Ebola virus RNA is associated with severe uveitis in a convalescent rhesus monkey
Gabriella Worwa, Timothy K. Cooper, Steven Yeh, Jessica G. Shantha, Amanda M.W. Hischak, Sarah E. Klim, Russell Byrum, Jonathan Kurtz, Scott M. Anthony, Nina M. Aiosa, Danny Ragland, Ji Hyun Lee, Marisa St. Claire, Carl W. Davis, Rafi Ahmed, Michael R. Holbrook, Jens H. Kuhn, Erica Ollmann Saphire, Ian Crozier
Abstract
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.