Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein.
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.
Schornberg
Kathryn
K
Department of Microbiology, University of Virginia, 1300 Jefferson Park Ave., Charlottesville, Virginia 22908-0734, USA.
Matsuyama
Shutoku
S
Kabsch
Kirsten
K
Delos
Sue
S
Bouton
Amy
A
White
Judith
J
D000818:Animals; D002401:Cathepsin B / Q000502:physiology*; D056668:Cathepsin L; D002403:Cathepsins / Q000502:physiology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000502:physiology*; D029043:Ebolavirus / Q000502:physiology*; D011992:Endosomes / Q000201:enzymology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014760:Viral Fusion Proteins / Q000502:physiology*
D034741:RNA, Small Interfering; D014760:Viral Fusion Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L