Role of Endosomal Cathepsins in Entry Mediated by the Ebola Virus Glycoprotein

Author:

Schornberg Kathryn1,Matsuyama Shutoku2,Kabsch Kirsten2,Delos Sue2,Bouton Amy1,White Judith12

Affiliation:

1. Departments of Microbiology

2. Cell Biology, University of Virginia, Charlottesville, Virginia 22908-0734

Abstract

ABSTRACT Using chemical inhibitors and small interfering RNA (siRNA), we have confirmed roles for cathepsin B (CatB) and cathepsin L (CatL) in Ebola virus glycoprotein (GP)-mediated infection. Treatment of Ebola virus GP pseudovirions with CatB and CatL converts GP1 from a 130-kDa to a 19-kDa species. Virus with 19-kDa GP1 displays significantly enhanced infection and is largely resistant to the effects of the CatB inhibitor and siRNA, but it still requires a low-pH-dependent endosomal/lysosomal function. These and other results support a model in which CatB and CatL prime GP by generating a 19-kDa intermediate that can be acted upon by an as yet unidentified endosomal/lysosomal enzyme to trigger fusion.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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