Document Detail


Characterization of fusion determinants points to the involvement of three discrete regions of both E1 and E2 glycoproteins in the membrane fusion process of hepatitis C virus.
MedLine Citation:
PMID:  17537855     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infection of eukaryotic cells by enveloped viruses requires the merging of viral and cellular membranes. Highly specific viral surface glycoproteins, named fusion proteins, catalyze this reaction by overcoming inherent energy barriers. Hepatitis C virus (HCV) is an enveloped virus that belongs to the genus Hepacivirus of the family Flaviviridae. Little is known about the molecular events that mediate cell entry and membrane fusion for HCV, although significant progress has been made due to recent developments in infection assays. Here, using infectious HCV pseudoparticles (HCVpp), we investigated the molecular basis of HCV membrane fusion. By searching for classical features of fusion peptides through the alignment of sequences from various HCV genotypes, we identified six regions of HCV E1 and E2 glycoproteins that present such characteristics. We introduced conserved and nonconserved amino acid substitutions in these regions and analyzed the phenotype of HCVpp generated with mutant E1E2 glycoproteins. This was achieved by (i) quantifying the infectivity of the pseudoparticles, (ii) studying the incorporation of E1E2 and their capacity to mediate receptor binding, and (iii) determining their fusion capacity in cell-cell and liposome/HCVpp fusion assays. We propose that at least three of these regions (i.e., at positions 270 to 284, 416 to 430, and 600 to 620) play a role in the membrane fusion process. These regions may contribute to the merging of viral and cellular membranes either by interacting directly with lipid membranes or by assisting the fusion process through their involvement in the conformational changes of the E1E2 complex at low pH.
Authors:
Dimitri Lavillette; Eve-Isabelle Pécheur; Peggy Donot; Judith Fresquet; Jennifer Molle; Romuald Corbau; Marlène Dreux; François Penin; François-Loïc Cosset
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-30
Journal Detail:
Title:  Journal of virology     Volume:  81     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-26     Completed Date:  2007-09-13     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8752-65     Citation Subset:  IM    
Affiliation:
Université de Lyon, IFR 128, F-69007 Lyon, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Hepacivirus / genetics,  physiology*
Humans
Membrane Fusion*
Molecular Sequence Data
Mutation
Viral Envelope Proteins / chemistry,  genetics,  metabolism*
Virion / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/E1 protein, Hepatitis C virus; 0/Viral Envelope Proteins; 157184-61-7/glycoprotein E2, Hepatitis C virus
Comments/Corrections

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