Viral haemorrhagic fever and vascular alterations

 

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Summary

Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/ macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells.

Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

Zusammenfassung

Die Pathogenese Virus-induzierter hämorrhagischer Fiebererkrankungen ist mit Gefäßstörungen verbunden. Die schwersten Virus-induzierten hämorrhagischen Fieber werden durch Filoviren (Marburg- und Ebola-Virus) ausgelöst und sollen hier im Vordergrund stehen. Monozyten/Makrophagen und dendritische Zellen werden nach Eintritt des Virus in den Körper primär infiziert. Während infizierte dendritische Zellen erheblich in ihrer immunmodulatorischen Funktion gestört werden und zu der bei Filovirusinfektionen beobachteten Immunsuppression beitragen, kann es nach Infektion von Monozyten/Makrophagen zu einer Überaktivierung kommen, die mit einer überschießenden Ausschüttung von Zytokinen und proinflammatorischen Mediatoren einhergeht. Diese freigesetzten Mediatoren führen zu pathologischen Regulationen des Gefäßsystems, insbesondere des Endothels.

Einige der zu Grunde liegenden molekularen Mechanismen der Endothelreaktionen werden diskutiert, z. B. die Regulation des vaskulären endothelialen Cadherin/Catenin- Komplexes der Zellkontakte, die Tyrosin-Phosphorylierung, die Expression von Zelladhäsionsmolekülen und des Tissue- Faktors sowie die Bedeutung von löslichen Virusproteinen auf das Gefäßsystem.

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