A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L

Virology. 2006 Mar 15;346(2):251-7. doi: 10.1016/j.virol.2006.01.007. Epub 2006 Feb 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin B / metabolism
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism*
  • Cell Fusion
  • Chlorocebus aethiops
  • Cricetinae
  • Cysteine Endopeptidases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Gene Silencing
  • Nipah Virus / physiology*
  • Protein Processing, Post-Translational*
  • Vero Cells
  • Viral Fusion Proteins / metabolism*


  • Enzyme Inhibitors
  • Viral Fusion Proteins
  • Cathepsins
  • Cysteine Endopeptidases
  • Cathepsin B
  • Cathepsin L