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PMID: 16460775 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Virology ·Vol. 346 ·No. 2 ·2006-03-15 ·Pages 251-7

Pager CT, Craft WW, Patch J, Dutch RE

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.

MeSH Terms
Animals Cathepsin B/metabolism Cathepsin L Cathepsins/antagonists & inhibitors,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
Chemicals
Enzyme Inhibitors Viral Fusion Proteins Cathepsins Cysteine Endopeptidases Cathepsin B Cathepsin L
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pager Cara Theresia
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
Patch Jared
Dutch Rebecca Ellis
References (29)
29 references, click to expand
  1. Nipah virus encephalitis reemergence, Bangladesh.
    Emerg Infect Dis. 2004 Dec;10(12):2082-7 PMID: 15663842
  2. Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9590-5 PMID: 12869695
  3. EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus.
    Nature. 2005 Jul 21;436(7049):401-5 PMID: 16007075
  4. Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing.
    Virology. 2005 Oct 10;341(1):130-40 PMID: 16083935
  5. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry.
    Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11876-81 PMID: 16081529
  6. Nipah virus: a recently emergent deadly paramyxovirus.
    Science. 2000 May 26;288(5470):1432-5 PMID: 10827955
  7. Endocytosis plays a critical role in proteolytic processing of the Hendra virus fusion protein.
    J Virol. 2005 Oct;79(20):12643-9 PMID: 16188966
  8. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection.
    Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12543-7 PMID: 16116101
  9. Ubiquitous activation of the Nipah virus fusion protein does not require a basic amino acid at the cleavage site.
    J Virol. 2004 Sep;78(18):9705-12 PMID: 15331703
  10. Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells.
    J Biol Chem. 2002 Jul 5;277(27):24609-17 PMID: 11986312
  11. Lysosomal cysteine proteases (cathepsins): promising drug targets.
    Acta Crystallogr D Biol Crystallogr. 2003 Feb;59(Pt 2):203-13 PMID: 12554931
  12. Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus.
    Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10652-7 PMID: 15998730
  13. The nipah virus fusion protein is cleaved within the endosomal compartment.
    J Biol Chem. 2005 Aug 19;280(33):29899-903 PMID: 15961384
  14. Endocytosis of the Nipah virus glycoproteins.
    J Virol. 2005 Mar;79(6):3865-72 PMID: 15731282
  15. Subcellular localization and calcium and pH requirements for proteolytic processing of the Hendra virus fusion protein.
    J Virol. 2004 Sep;78(17):9154-63 PMID: 15308711
  16. Treatment of acute Nipah encephalitis with ribavirin.
    Ann Neurol. 2001 Jun;49(6):810-3 PMID: 11409437
  17. Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter.
    J Virol. 1999 Jan;73(1):251-9 PMID: 9847328
  18. Isolation of Nipah virus from Malaysian Island flying-foxes.
    Microbes Infect. 2002 Feb;4(2):145-51 PMID: 11880045
  19. Molecular characterization of Nipah virus, a newly emergent paramyxovirus.
    Virology. 2000 Jun 5;271(2):334-49 PMID: 10860887
  20. The cleavage activation and sites of glycosylation in the fusion protein of Hendra virus.
    Virus Res. 2000 Sep 25;69(2):83-93 PMID: 11018278
  21. A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor.
    Mol Cell. 2004 Apr 23;14(2):207-19 PMID: 15099520
  22. Processing of the Ebola virus glycoprotein by the proprotein convertase furin.
    Proc Natl Acad Sci U S A. 1998 May 12;95(10):5762-7 PMID: 9576958
  23. Inhibition of Henipavirus fusion and infection by heptad-derived peptides of the Nipah virus fusion glycoprotein.
    Virol J. 2005 Jul 18;2:57 PMID: 16026621
  24. Cathepsin L is involved in proteolytic processing of the Hendra virus fusion protein.
    J Virol. 2005 Oct;79(20):12714-20 PMID: 16188974
  25. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection.
    Science. 2005 Jun 10;308(5728):1643-5 PMID: 15831716
  26. Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones.
    Biochimie. 1994;76(3-4):217-25 PMID: 7819326
  27. Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus.
    Science. 1998 Apr 17;280(5362):450-3 PMID: 9545226
  28. Abnormal glycosylation of procathepsin L due to N-terminal point mutations correlates with failure to sort to lysosomes.
    J Biol Chem. 1997 Mar 28;272(13):8808-16 PMID: 9079717
  29. Membrane fusion tropism and heterotypic functional activities of the Nipah virus and Hendra virus envelope glycoproteins.
    J Virol. 2002 Nov;76(22):11186-98 PMID: 12388678
Article Info
Journal
Virology
Abbr.
Virology
ISSN
0042-6822
DOI
10.1016/j.virol.2006.01.007
Published
2006-03-15
Epub
2006-00-07
Pages
251-7
Language
English
Region
United States
NLM ID
0110674
PMCID
PMC7111743
Subset
IM
Grants
NIAID NIH HHS · R01 AI051517 · United States
NIAID NIH HHS · R21 AI063052 · United States
NIAID NIH HHS · AI063052 · United States
External Links
PubMed source DOI: 10.1016/j.virol.2006.01.007 PMC Full Text View journal details
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