Virology: Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection

Kartik Chandran, Nancy J. Sullivan, Ute Felbor, Sean P. Whelan, James M. Cunningham

Research output: Contribution to journalArticle

546 Citations (Scopus)

Abstract

Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs.

Original languageEnglish (US)
Pages (from-to)1643-1645
Number of pages3
JournalScience
Volume308
Issue number5728
DOIs
StatePublished - Jun 10 2005
Externally publishedYes

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Ebolavirus
Virology
Proteolysis
Cathepsin B
Glycoproteins
Cathepsin L
Infection
Cercopithecus aethiops
Vesicular Stomatitis
Vero Cells
Cysteine Proteases
Protease Inhibitors
Cultured Cells
Peptide Hydrolases
Fever
Viruses
Kidney
Cell Line
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Chandran, K., Sullivan, N. J., Felbor, U., Whelan, S. P., & Cunningham, J. M. (2005). Virology: Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection. Science, 308(5728), 1643-1645. https://doi.org/10.1126/science.1110656

Virology : Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection. / Chandran, Kartik; Sullivan, Nancy J.; Felbor, Ute; Whelan, Sean P.; Cunningham, James M.

In: Science, Vol. 308, No. 5728, 10.06.2005, p. 1643-1645.

Research output: Contribution to journalArticle

Chandran, K, Sullivan, NJ, Felbor, U, Whelan, SP & Cunningham, JM 2005, 'Virology: Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection', Science, vol. 308, no. 5728, pp. 1643-1645. https://doi.org/10.1126/science.1110656
Chandran, Kartik ; Sullivan, Nancy J. ; Felbor, Ute ; Whelan, Sean P. ; Cunningham, James M. / Virology : Endosomal proteolysis of the ebola virus glycoprotein is necessary for infection. In: Science. 2005 ; Vol. 308, No. 5728. pp. 1643-1645.
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