Pathogenesis of Ebola Hemorrhagic Fever in Primate Models: Evidence that Hemorrhage Is Not a Direct Effect of Virus-Induced Cytolysis of Endothelial Cells

Thomas Geisbert, Howard A. Young, Peter B. Jahrling, Kelly J. Davis, Tom Larsen, Elliott Kagan, Lisa E. Hensley

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Ebola virus (EBOV) infection causes a severe and often fatal hemorrhagic disease in humans and nonhuman primates. Whether infection of endothelial cells is central to the pathogenesis of EBOV hemorrhagic fever (HF) remains unknown. To clarify the role of endothelial cells in EBOV HF, we examined tissues of 21 EBOV-infected cynomolgus monkeys throughout time, and also evaluated EBOV infection of primary human umbilical vein endothelial cells and primary human lung-derived microvascular endothelial cells in vitro. Results showed that endothelial cells were not early cellular targets of EBOV in vivo, as viral replication was not consistently observed until day 5 after infection, a full day after the onset of disseminated intravascular coagulation. Moreover, the endothelium remained relatively intact even at terminal stages of disease. Although human umbilical vein endothelial cells and human lung-derived microvascular endothelial cells were highly permissive to EBOV replication, significant cytopathic effects were not observed. Analysis of host cell gene response at 24 to 144 hours after infection showed some evidence of endothelial cell activation, but changes were unremarkable considering the extent of viral replication. Together, these data suggest that coagulation abnormalities associated with EBOV HF are not the direct result of EBOV-induced cytolysis of endothelial cells, and are likely triggered by immune-mediated mechanisms.

Original languageEnglish (US)
Pages (from-to)2371-2382
Number of pages12
JournalAmerican Journal of Pathology
Volume163
Issue number6
StatePublished - Dec 2003
Externally publishedYes

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Ebola Hemorrhagic Fever
Ebolavirus
Primates
Endothelial Cells
Hemorrhage
Viruses
Human Umbilical Vein Endothelial Cells
Infection
Lung
Macaca fascicularis
Disseminated Intravascular Coagulation
Virus Replication
Endothelium

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pathogenesis of Ebola Hemorrhagic Fever in Primate Models : Evidence that Hemorrhage Is Not a Direct Effect of Virus-Induced Cytolysis of Endothelial Cells. / Geisbert, Thomas; Young, Howard A.; Jahrling, Peter B.; Davis, Kelly J.; Larsen, Tom; Kagan, Elliott; Hensley, Lisa E.

In: American Journal of Pathology, Vol. 163, No. 6, 12.2003, p. 2371-2382.

Research output: Contribution to journalArticle

Geisbert, Thomas ; Young, Howard A. ; Jahrling, Peter B. ; Davis, Kelly J. ; Larsen, Tom ; Kagan, Elliott ; Hensley, Lisa E. / Pathogenesis of Ebola Hemorrhagic Fever in Primate Models : Evidence that Hemorrhage Is Not a Direct Effect of Virus-Induced Cytolysis of Endothelial Cells. In: American Journal of Pathology. 2003 ; Vol. 163, No. 6. pp. 2371-2382.
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