Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses

Abstract

Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered.

Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care

“…Glomerular and tubular necrosis in addition to interstitial lymphocytosis have been documented post mortem in kidney tissues of patients who died of Ebola virus disease. 19 On admission, our patient was severely volume depleted, which probably contributed to his kidney failure.…”

Post-exposure treatments for Ebola and Marburg virus infections

“…Filoviruses have a broad cell tropism and productively replicate in numerous cell types. Electron microscopic examination of tissues from experimentally infected NHPs and from fatal human cases has demonstrated that monocytes, macrophages, dendritic cells, hepatocytes, adrenal cortical cells, endothelial cells, fibroblasts and several types of epithelial cell can all support replication of filoviruses [40][41][42][43][44][45][46][47][48][49][50][51][52][53] . Systematic studies in experimentally infected NHPs suggest that monocytes, macrophages and dendritic cells are the early replication sites for EBOV and MARV 41,48,51 .…”

Neurological Complications of Ebola Virus Infection

“…They can either directly infect humans or the bats may infect wild animals that may then serve as an intermediary host. Humanto-human transmission is the major cause of the spread of the infection [5]. The virus is shed in all bodily fluids, including saliva, tears, sweat, urine, semen, and even ear wax.…”