title: Y-box-binding protein 1 interacts with hepatitis C virus NS3/4A and influences the equilibrium between viral RNA replication and infectious particle production.
abstract: The hepatitis C virus (HCV) NS3/4A protein has several essential roles in the virus life cycle, most probably through dynamic interactions with host factors. To discover cellular cofactors that are co-opted by HCV for its replication, we elucidated the NS3/4A interactome using mass spectrometry and identified Y-box-binding protein 1 (YB-1) as an interacting partner of NS3/4A protein and HCV genomic RNA. Importantly, silencing YB-1 expression decreased viral RNA replication and severely impaired the propagation of the infectious HCV molecular clone JFH-1. Immunofluorescence studies further revealed a drastic HCV-dependent redistribution of YB-1 to the surface of the lipid droplets, an important organelle for HCV assembly. Core and NS3 protein-dependent polyprotein maturation were shown to be required for YB-1 relocalization. Unexpectedly, YB-1 knockdown cells showed the increased production of viral infectious particles while HCV RNA replication was impaired. Our data support that HCV hijacks YB-1-containing ribonucleoparticles and that YB-1-NS3/4A-HCV RNA complexes regulate the equilibrium between HCV RNA replication and viral particle production.
authors.affiliation: Institut de Recherche en Immunologie et en Cancérologie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chatel-Chaix
authors.forename: Pierre
authors.initials: P
authors.lastname: Melançon
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Racine
authors.forename: Martin
authors.initials: M
authors.lastname: Baril
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamarre
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D047908:Intracellular Signaling Peptides and Proteins; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D012367:RNA, Viral / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D051840:Y-Box-Binding Protein 1; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus