Endosomal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection

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 pr...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2005-06, Vol.308 (5728), p.1643-1645
Main Authors: Chandran, Kartik, Sullivan, Nancy J, Felbor, Ute, Whelan, Sean P, Cunningham, James M
Format: Article
Language:English
Subjects:
Analysis
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biochemistry
Biological and medical sciences
Cathepsin B - antagonists & inhibitors
Cathepsin B - metabolism
Cathepsin L
Cathepsins - antagonists & inhibitors
Cathepsins - metabolism
Cell Line
Cell lines
Cell membranes
Cells
Cells, Cultured
Cercopithecus aethiops
Cysteine Endopeptidases - metabolism
Cysteine Proteinase Inhibitors - pharmacology
Diagnosis
Ebola virus
Ebolavirus - metabolism
Ebolavirus - physiology
Endosomes - metabolism
Enzymes
Glycoproteins
Human viral diseases
Hydrogen-Ion Concentration
Infections
Infectious diseases
Marburg disease, ebola disease
Medical sciences
Medical treatment
Mice
Pharmacology. Drug treatments
Protease inhibitors
Tropical viral diseases
Vero Cells
Vesicular stomatitis Indiana virus - genetics
Vesicular stomatitis Indiana virus - physiology
Viral diseases
Viral Envelope Proteins - metabolism
Virion - physiology
Viruses
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1110656