Ebola and Marburg Viruses: Pathogenesis and Development of Countermeasures

Lisa   E.   Hensley; Steven   M.   Jones; Heinz      Feldmann; Peter   B.   Jahrling; Thomas   W.   Geisbert

Abstract

Ebola and Marburg viruses, family Filoviridae, are among the best known examples of emerging and re-emerging pathogens. Although outbreaks have been sporadic and geographically restricted to areas of Central Africa, the hemorrhagic fevers caused by these viruses are remarkably severe and are associated with high case fatality rates often exceeding 80 percent. In addition to humans, these viruses have decimated populations of wild apes in Central Africa. Currently, there are no vaccines or effective therapies available for human use. Progress in understanding the geneses of the pathophysiological changes that make filoviral infections of humans so destructive has been slow, primarily because these viruses require special containment for safe research. However, an increasing understanding of the molecular mechanisms of filoviral pathogenesis, facilitated by the development of new tools to elucidate critical regulatory elements in the viral life cycle, is providing new targets that can be exploited for therapeutic interventions. In addition, substantial progress has been made in developing recombinant vaccines against these viruses.

Keywords: filoviral particles, furin-like endoprotease, ICAM, TNF-related apoptosis-inducing ligand (TRAIL), coagulation defects, proinflammatory

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