Association of Ebola-related Reston virus particles and antigen with tissue lesions of monkeys imported to the United States

During 1989-1990, an epizootic involving a filovirus closely related to Ebola virus occurred in a Reston, Virginia, primate-holding facility. Tissues were collected from cynomolgus monkeys and examined by electron microscopy and immunohistochemistry for Ebola-related viral antigen. Viral replication was extensive in fixed tissue macrophages, interstitial fibroblasts of many organs, circulating macrophages and monocytes, and was observed less frequently in vascular endothelial cells, hepatocytes, adrenal cortical cells and renal tubular epithelium. Viral replication was observed infrequently in epithelial cells lining ducts or mucous membranes, intestinal epithelial cells, eosinophils and plasma cells. Replication of Reston virus in lymphocytes was never observed, in contrast to reports of lymphocytes of monkeys experimentally infected with the Ebola-Zaire virus. Free filoviral particles were seen in pulmonary alveoli and renal tubular lumina, which correlates with epidemiological evidence of droplet and fomite transmission. Viral infection of interstitial fibroblasts and macrophages caused multisystemic disruptive lesions involving connective tissue. Focal necrosis in organs where viral replication was minimal may have been secondary to ischaemia caused by fibrin deposition and occasional platelet-fibrin thrombi. Immunoelectron microscopy on sections of liver, differentiated viral tubular inclusion masses and precursor material from non-viral tubuloreticular inclusions. Immunohistochemistry showed that the distribution of viral antigen in affected tissue correlated well with ultrastructural localization of virions.