title: 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.
authors.affiliation: Infectious Diseases Pathology Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Roosecelis Brasil
authors.initials: RB
authors.lastname: Martines
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Ng
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Greer
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Rollin
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
mesh_terms: D000818:Animals; D001706:Biopsy; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D019142:Hemorrhagic Fever, Ebola / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000473:pathology* / Q000635:transmission / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008379:Marburg Virus Disease / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000473:pathology* / Q000635:transmission / Q000821:virology*; D029024:Marburgvirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D057089:Pathology, Molecular / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D056189:Viral Tropism; D014773:Virology / Q000379:methods; D014774:Virulence; D053586:Virus Internalization
keywords: Ebola virus; Marburg virus; autopsy; electron microscopy; filovirus; haemorrhagic fever; immunohistochemistry; pathogenesis; pathology