A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L.
The Nipah virus fusion (F) protein is proteolytically processed to F1 + F2 subunits. We demonstrate here that cathepsin L is involved in this important maturation event. Cathepsin inhibitors ablated cleavage of Nipah F. Proteolytic processing of Nipah F and fusion activity was dramatically reduced in cathepsin L shRNA-expressing Vero cells. Additionally, Nipah virus F-mediated fusion was inhibited in cathepsin L-deficient cells, but coexpression of cathepsin L restored fusion activity. Both purified cathepsin L and B could cleave immunopurified Nipah F protein, but only cathepsin L produced products of the correct size. Our results suggest that endosomal cathepsins can cleave Nipah F, but that cathepsin L specifically converts Nipah F to a mature and fusogenic form.
Pager
Cara Theresia
CT
Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Biomedical Biological Sciences Research Building, 741 South Limestone, Lexington, KY 40536-0509, USA.
Craft
Willie Warren
WW
Patch
Jared
J
Dutch
Rebecca Ellis
RE
D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020868:Gene Silencing; D045405:Nipah Virus / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D014760:Viral Fusion Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L