Document Detail


Activation of the Nipah virus fusion protein in MDCK cells is mediated by cathepsin B within the endosome-recycling compartment.
MedLine Citation:
PMID:  22278224     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proteolytic activation of the fusion protein of the highly pathogenic Nipah virus (NiV F) is a prerequisite for the production of infectious particles and for virus spread via cell-to-cell fusion. Unlike other paramyxoviral fusion proteins, functional NiV F activation requires endocytosis and pH-dependent cleavage at a monobasic cleavage site by endosomal proteases. Using prototype Vero cells, cathepsin L was previously identified to be a cleavage enzyme. Compared to Vero cells, MDCK cells showed substantially higher F cleavage rates in both NiV-infected and NiV F-transfected cells. Surprisingly, this could not be explained either by an increased F endocytosis rate or by elevated cathepsin L activities. On the contrary, MDCK cells did not display any detectable cathepsin L activity. Though we could confirm cathepsin L to be responsible for F activation in Vero cells, inhibitor studies revealed that in MDCK cells, cathepsin B was required for F-protein cleavage and productive replication of pathogenic NiV. Supporting the idea of an efficient F cleavage in early and recycling endosomes of MDCK cells, endocytosed F proteins and cathepsin B colocalized markedly with the endosomal marker proteins early endosomal antigen 1 (EEA-1), Rab4, and Rab11, while NiV F trafficking through late endosomal compartments was not needed for F activation. In summary, this study shows for the first time that endosomal cathepsin B can play a functional role in the activation of highly pathogenic NiV.
Authors:
Sandra Diederich; Lucie Sauerhering; Michael Weis; Hermann Altmeppen; Norbert Schaschke; Thomas Reinheckel; Stephanie Erbar; Andrea Maisner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-25
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-12     Completed Date:  2012-06-11     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3736-45     Citation Subset:  IM    
Affiliation:
Institute of Virology, Philipps University of Marburg, Marburg, Germanya; Faculty of Chemistry, University of Bielefeld, Bielefeld, Germany. maisner@staff.uni-marburg.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Cathepsin B / genetics,  metabolism*
Cathepsin L / genetics,  metabolism
Cell Line
Dogs
Endocytosis
Endosomes / enzymology*,  virology
Henipavirus Infections / enzymology*,  genetics,  physiopathology,  virology*
Humans
Mice
Mice, Knockout
Nipah Virus / genetics,  metabolism*
Viral Fusion Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Viral Fusion Proteins; EC 3.4.22.1/Cathepsin B; EC 3.4.22.15/Cathepsin L
Comments/Corrections

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