Endosomal Proteolysis of the Ebola Virus Glycoprotein is Necessary for Infection

Overview

Journal Science

Specialty Science

Date 2005 Apr 16

PMID 15831716

Citations 543

Authors

Kartik Chandran

Nancy J Sullivan

Ute Felbor

Sean P Whelan

James M Cunningham

Affiliations

Soon will be listed here.

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.

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