title: A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L.
abstract: 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.
authors.affiliation: 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.
authors.forename: Cara Theresia
authors.initials: CT
authors.lastname: Pager
authors.forename: Willie Warren
authors.initials: WW
authors.lastname: Craft
authors.forename: Jared
authors.initials: J
authors.lastname: Patch
authors.forename: Rebecca Ellis
authors.initials: RE
authors.lastname: Dutch
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D014760:Viral Fusion Proteins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L