title: The deletion of residues 268-292 of E1 impairs the ability of HCV envelope proteins to induce pore formation.
abstract: We have obtained a chimeric protein containing the ectodomains of hepatitis C virus (HCV) envelope proteins but lacking the region 268-292 of E1. All its structural properties are coincident with those of the corresponding full length chimera. The deleted and entire chimeras were compared in terms of their membrane destabilizing properties. No differences were found in their ability to induce vesicle aggregation and lipid mixing but the deleted chimera showed a reduced capacity to promote leakage. The role of the deletion was also studied by obtaining HCV pseudoparticles (HCVpp). Both E1 and E2, and also the E1 deleted mutant, were incorporated into HCVpp to a similar level. However, HCVpp containing the E1 deleted protein are almost unable to infect Huh7 cells. These results point to the involvement of the region 268-292 in the formation of pores in the membrane necessary for the complete fusion of the membranes.
authors.affiliation: Department of Biochemistry and Molecular Biology, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Lombana
authors.affiliation: Department of Biochemistry and Molecular Biology, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ortega-Atienza
authors.affiliation: Department of Biochemistry and Molecular Biology, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Gómez-Gutiérrez
authors.affiliation: Department of Biochemistry and Molecular Biology, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Yélamos
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.affiliation: Department of Biochemistry and Molecular Biology, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: pacog@bbm1.ucm.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gavilanes
mesh_terms: D000595:Amino Acid Sequence; D057809:HEK293 Cells; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008081:Liposomes; D016296:Mutagenesis; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D053586:Virus Internalization
chemical_list: C087035:E1 protein, Hepatitis C virus; D008081:Liposomes; D014759:Viral Envelope Proteins
keywords: Hepatitis C virus; Lipid-protein interaction; Membrane fusion; Protein spectroscopic properties; Viral envelope proteins