Document Detail


Acid-activated structural reorganization of the Rift Valley fever virus Gc fusion protein.
MedLine Citation:
PMID:  23035232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The entry of the enveloped Rift Valley fever virus (RVFV) into its host cell is mediated by the viral glycoproteins Gn and Gc. We investigated the RVFV entry process and, in particular, its pH-dependent activation mechanism using our recently developed nonspreading-RVFV-particle system. Entry of the virus into the host cell was efficiently inhibited by lysosomotropic agents that prevent endosomal acidification and by compounds that interfere with dynamin- and clathrin-dependent endocytosis. Exposure of plasma membrane-bound virions to an acidic pH (<pH 6) equivalent to the pH of late endolysosomal compartments allowed the virus to bypass the endosomal route of infection. Acid exposure of virions in the absence of target membranes triggered the class II-like Gc fusion protein to form extremely stable oligomers that were resistant to SDS and temperature dissociation and concomitantly compromised virus infectivity. By targeted mutagenesis of conserved histidines in Gn and Gc, we demonstrated that mutation of a single histidine (H857) in Gc completely abrogated virus entry, as well as acid-induced Gc oligomerization. In conclusion, our data suggest that after endocytic uptake, RVFV traffics to the acidic late endolysosomal compartments, where histidine protonation drives the reorganization of the Gc fusion protein that leads to membrane fusion.
Authors:
S M de Boer; J Kortekaas; L Spel; P J M Rottier; R J M Moormann; B J Bosch
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-01-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13642-52     Citation Subset:  IM    
Affiliation:
Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Acids / metabolism*
Animals
Base Sequence
Blotting, Western
Cell Line
Cricetinae
DNA Primers
Drosophila
Electrophoresis, Polyacrylamide Gel
Endocytosis
Flow Cytometry
Hydrogen-Ion Concentration
Microscopy, Fluorescence
Protein Conformation
Rift Valley fever virus / metabolism*
Viral Fusion Proteins / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Acids; 0/DNA Primers; 0/Viral Fusion Proteins
Comments/Corrections

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