Filoviruses infect rhesus macaque synoviocytes in vivo and primary human synoviocytes in vitro

The most commonly reported symptom of post-Ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent Ebola virus infection has not been well-characterized in human patients or animal models. By immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by Ebola virus/Kikwit, Ebola virus/Makona-C05, and Marburg virus/Angola in the rhesus macaque model. Further, we demonstrate by histology, immunohistochemistry, RNAscope in situ hybridization, and transmission electron microscopy that synoviocytes of the stifle, shoulder, and hip are a target for mouse-adapted Ebola virus/Yambuku-Mayinga infection during acute disease in rhesus macaques. A time course of infection study with Ebola virus/Kikwit found large joint synovium became immunopositive beginning on post-infection day 6. In total, the synovium of 28/30 rhesus macaques with terminal filovirus disease had evidence of infection (64/96 joints examined). By immunofluorescence, infected cell types included both CD68+ type A (macrophage-like) synoviocytes and CD44+ type B (fibroblast-like) synoviocytes. Cultured primary human fibroblast-like synoviocytes were permissive to infection with Ebola and Marburg viruses in vitro. Because synovial joints include immune privileged sites, these findings are significant for future investigations of filovirus pathogenesis and persistence as well as arthralgias in acute and convalescent filovirus disease. Copyright © 2020. Published by Elsevier Inc.

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