Pathogenesis of Marburg Hemorrhagic Fever in Cynomolgus Macaques

Abstract

The sequence of pathogenic events identified in this study provides an understanding of the development of disease processes and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

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 .…”

“…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 . Filovirus infection of mononuclear phagocytes is thought to trigger a series of events that includes the production and release of the procoagulant protein tissue factor 54,55 and an assortment of pro-inflammatory cytokines, chemokines and free radical species in NHPs and humans 48,51,[55][56][57][58][59][60][61][62][63][64][65][66][67][68] .…”

“…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 . Filovirus infection of mononuclear phagocytes is thought to trigger a series of events that includes the production and release of the procoagulant protein tissue factor 54,55 and an assortment of pro-inflammatory cytokines, chemokines and free radical species in NHPs and humans 48,51,[55][56][57][58][59][60][61][62][63][64][65][66][67][68] . This dysregulated host response likely plays a greater role in the development of the observed pathology than any structural damage caused by viral replication in host cells and/or tissues.…”

“…Results from many studies have shown biochemical and histological evidence of disseminated intravascular coagulation in both experimentally infected NHPs and humans 19,20,22,23,40,[44][45][46][49][50][51]53,54,70,[73][74][75][76][77][78][79] . The mechanisms that cause these coagulation disorders are not fully understood, but the expression or release of tissue factor from filovirus-infected monocytes and macro phages seems to play a role 54,55 .…”

A bioluminescent imaging mouse model for Marburg virus based on a pseudovirus system

“…19,20 Non-human primates are the most reliable model because the clinical symptoms and pathophysiology are quite similar to those observed in humans. 21 However, the cost and time associated with model are prohibitive for the high-throughput screening of drugs and the early evaluation of vaccines. Serial passages of the original MARV endue it lethal infection capacity to rodents, whereas the disease course still differs from that of humans.…”