Title :

Functional Study of the C-Terminal Part of the Hepatitis C Virus E1 Ectodomain

Author(s) :

Moustafa, Rehab [Auteur]
National Research Centre - NRC (EGYPT)
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Haddad, Juliano [Auteur]
الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth] [LU / ULB]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Linna, Lydia [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Hanoulle, Xavier [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Descamps, Véronique [Auteur]
Unité de Virologie clinique et fondamentale [UVCF]
Mesalam, Ahmed Atef [Auteur]
National Research Centre - NRC (EGYPT)
Universiteit Gent = Ghent University = Université de Gand [UGENT]
Baumert, Thomas [Auteur]
Institut de Recherche sur les Maladies Virales et Hépatiques [IVH]
Duverlie, Gilles [Auteur]
Institut de biologie de Lille - UMS 3702 [IBL]
Meuleman, Philip [Auteur]
Universiteit Gent = Ghent University = Université de Gand [UGENT]
Dubuisson, Jean [Auteur]
Institut de biologie de Lille - UMS 3702 [IBL]
Lavie, Muriel [Auteur]
Institut de biologie de Lille - UMS 3702 [IBL]

Journal title :

Journal of virology

Pages :

e00939-18

Publisher :

American Society for Microbiology

Publication date :

2018

ISSN :

0022-538X

English keyword(s) :

hepatitis C virus
glycoprotein
envelope proteins
viral entry
viral assembly

HAL domain(s) :

Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie

English abstract : [en]

In the hepatitis C virus (HCV) envelope glycoproteins E1 and E2, which form a heterodimer, E2 is the receptor binding protein and the major target of neutralizing antibodies, whereas the function of E1 remains less ...
Show more >In the hepatitis C virus (HCV) envelope glycoproteins E1 and E2, which form a heterodimer, E2 is the receptor binding protein and the major target of neutralizing antibodies, whereas the function of E1 remains less characterized. To investigate E1 functions, we generated a series of mutants in the conserved residues of the C-terminal region of the E1 ectodomain in the context of an infectious clone. We focused our analyses on two regions of interest. The first region is located in the middle of the E1 glycoprotein (between amino acid [aa] 270 and aa 291), which contains a conserved hydrophobic sequence and was proposed to constitute a putative fusion peptide. The second series of mutants was generated in the region from aa 314 to aa 342 (the aa314-342 region), which has been shown to contain two α helices (α2 and α3) by nuclear magnetic resonance studies. Of the 22 generated mutants, 20 were either attenuated or noninfectious. Several mutations modulated the virus's dependence on claudin-1 and the scavenger receptor BI coreceptors for entry. Most of the mutations in the putative fusion peptide region affected virus assembly. Conversely, mutations in the α-helix aa 315 to 324 (315-324) residues M318, W320, D321, and M322 resulted in a complete loss of infectivity without any impact on E1E2 folding and on viral assembly. Further characterization of the W320A mutant in the HCVpp model indicated that the loss of infectivity was due to a defect in viral entry. Together, these results support a role for E1 in modulating HCV interaction with its coreceptors and in HCV assembly. They also highlight the involvement of α-helix 315-324 in a late step of HCV entry.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Identification of host factors involved in Hepatitis C Virus assembly and characterization of their potential role in vivo

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL