Fiche publication
Date publication
septembre 2014
Journal
Journal of virology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Lavie M, Sarrazin S, Montserret R, Descamps V, Baumert TF, Duverlie G, Séron K, Penin F, Dubuisson J
Lien Pubmed
Résumé
In spite of the high variability of its sequence, hepatitis C virus (HCV) envelope glycoprotein E2 contains several conserved regions. In this study, we explored the structural and functional features of the highly conserved E2 segment from amino acid (aa) 502 to 520, which had been proposed as a fusion peptide and shown to strongly overlap a potential conserved neutralizing epitope. For this purpose, we used reverse genetics to introduce point mutations within this region, and we characterized the phenotypes of these mutants in the light of the recently published structure of E2. The functional analyses showed that their phenotypes are in agreement with the positions of the corresponding residues in the E2 crystal structure. In contrast, our data ruled out the involvement of this region in membrane fusion, and they indicate that alternative conformations would be necessary to expose the potential neutralizing epitope present in this segment. Of particular interest, we identified three specific mutations (Y507L, V514A, and V515A) located within this neutralizing epitope which only mildly reduced infectivity and showed no assembly defect. These mutations modulated HCV dependence on the viral receptor SRB1, and/or they also modulated virion sensitivity to neutralizing antibodies. Importantly, their characterization also showed that amino acids Y507, V514, and V515 contribute to E2 interaction with HCV receptor CD81. In conclusion, our data show that the highly conserved E2 segment from aa 502 to 520 plays a key role in cell entry by influencing the association of the viral particle with coreceptors and neutralizing antibodies.
Mots clés
Amino Acid Sequence, Conserved Sequence, Hepacivirus, chemistry, Hepatitis C, genetics, Humans, Models, Molecular, Protein Binding, Receptors, Virus, genetics, Scavenger Receptors, Class B, genetics, Sequence Alignment, Tetraspanin 28, genetics, Viral Envelope Proteins, chemistry, Virus Internalization
Référence
J. Virol.. 2014 Sep;88(18):10584-97
