The Nipah virus fusion (F) protein is proteolytically processed to F 1 + 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.
|Number of pages||7|
|State||Published - Mar 15 2006|
Bibliographical noteFunding Information:
We would like to thank Dr. Lin-fa Wang (Australian Animal Health Laboratory) for the Nipah F and G plasmids; Drs. Paul Selleck and Chris Morrissy for the anti-gamma inactivated Nipah virus antiserum (Australian Animal Health Laboratory); Dr. Doug Andres (University of Kentucky) for the pSuper-Scramble plasmid; Karl-Klaus Conzelman (Pettenkofer Institut) for the BSR cells; and Dr. Terence Dermody (Vanderbilt University) for the cathepsin L MEFs and pSG5-cathepsin L vector. We greatly appreciate assistance from Jennifer Strange in the UK Flow Cytometry Core Facility. We are grateful to members of the Dutch lab and Dr. Christopher Broder for critically reviewing the manuscript. C.T.P. and W.W.C. are recipients of an AHA Ohio Valley Affiliate predoctoral fellowship and a Ruth L. Kirshechstein National Research Service Award, respectively. This study was supported by NIAID grant AI063052 to R.E.D.
- Cathepsin L
- Fusion protein
- Proteolytic processing
ASJC Scopus subject areas