title: Interfering with hepatitis C virus assembly in vitro using affinity peptides directed towards core protein.
abstract: Viral assembly is a crucial key step in the life cycle of every virus. In the case of Hepatitis C virus (HCV), the core protein is the only structural protein to interact directly with the viral genomic RNA. Purified recombinant core protein is able to self-assemble in vitro into nucleocapsid-like particles upon addition of a structured RNA, providing a robust assay with which to study HCV assembly. Inhibition of self-assembly of the C170 core protein (first 170 amino acids) was tested using short peptides derived from the HCV core, from HCV NS5A protein, and from diverse proteins (p21 and p73) known to interact with HCV core protein. Interestingly, peptides derived from the core were the best inhibitors. These peptides are derived from regions of the core predicted to be involved in the interaction between core subunits during viral assembly. We also demonstrated that a peptide derived from the C-terminal end of NS5A protein moderately inhibits the assembly process.
authors.affiliation: PROTEO, IBIS and Department of Biochemistry and Microbiology, Université Laval, Québec, QC G1V 0A6, Canada.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Duvignaud
authors.forename: Nathalie
authors.initials: N
authors.lastname: Majeau
authors.forename: Priscilla
authors.initials: P
authors.lastname: Delisle
authors.forename: Normand
authors.initials: N
authors.lastname: Voyer
authors.forename: Stéphane M
authors.initials: SM
authors.lastname: Gagné
authors.forename: Denis
authors.initials: D
authors.lastname: Leclerc
mesh_terms: D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019251:Nucleocapsid / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D019065:Virus Assembly / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D010455:Peptides; D012367:RNA, Viral; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase