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Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein
Kathryn Schornberg1, Shutoku Matsuyama, Kirsten Kabsch
1Department of Microbiology, University of Virginia, 1300 Jefferson Park Ave., Charlottesville, Virginia 22908-0734, USA.
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.
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