Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury

Zhi Yong Yang, Henricus J. Duckers, Nancy J. Sullivan, Anthony Sanchez, Elizabeth G. Nabel, Gary J. Nabel

Research output: Contribution to journalArticle

Abstract

Here we defined the main viral determinant of Ebola virus pathogenicity; synthesis of the virion glycoprotein (GP) of Ebola virus Zaire induced cytotoxic effects in human endothelial cells in vitro and in vivo. This effect mapped to a serine-threonine-rich, mucin-like domain of this type I trans-membrane glycoprotein, one of seven gene products of the virus. Gene transfer of GP into explanted human or porcine blood vessels caused massive endothelial cell loss within 48 hours that led to a substantial increase in vascular permeability. Deletion of the mucin-like region of GP abolished these effects without affecting protein expression or function. GP derived from the Reston strain of virus, which causes disease in nonhuman primates but not in man, did not disrupt the vasculature of human blood vessels. In contrast, the Zaire GP induced endothelial cell disruption and cytotoxicity in both nonhuman primate and human blood vessels, and the mucin domain was required for this effect. These findings indicate that GP, through its mucin domain, is the viral determinant of Ebola pathogenicity and likely contributes to hemorrhage during infection.

Original languageEnglish (US)
Pages (from-to)886-889
Number of pages4
JournalNature Medicine
Volume6
Issue number8
DOIs
StatePublished - Aug 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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