143 - Hemorrhagic Fevers: Endothelial Cells and Ebola-Virus Hemorrhagic Fever

Summary

Viral hemorrhagic fever (VHF) is a severe multiorgan disease with strong immune involvement and diffuse vascular dysregulation, particularly of the vascular endothelium. Several families of RNA viruses are regularly associated with a VHF syndrome in humans: Arenaviridae (Lassa virus, Machupo virus, Junin virus, Guanarito virus, and Sabia virus), Bunyaviridae (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, hantaviruses), Flaviviridae (Yellow fever virus, Dengue virus, Omsk hemorrhagic fever virus, and Kyasanur forest disease virus), and Filoviridae (Marburg virus and Ebola virus). The clinical manifestations of VHF vary and are dependent on the causative agent (see CDC homepage http://www.cdc.gov). However, some common clinical features include fever, various degrees of vascular dysregulation with bleeding tendency and shock development, and the vascular endothelium seems to be affected in most cases (1–3). Some of the VHF-causing pathogens target the endothelium directly, whereas others induce primarily indirect alterations through proinflammatory mediators released from infected target cells (e.g., monocytes/macrophages). Marburg (MARV) and Ebola viruses (EBOV) cause the most severe form of VHF and, thus, serve as important model pathogens for studying the pathogenesis and management of VHFs. Filoviruses, as well as some other hemorrhagic fever (HF) viruses, are biological safety level 4 (BSL4) agents, which somewhat complicates investigations. Filoviruses seem to target both the vascular system and the immune system, leading to the opinion that filovirus HF fever is a vascular disease as well as an immune syndrome (2–5). Although our understanding of the molecular mechanisms of VHF pathogenesis is still limited, some important scientific achievements have been made in the past decade.