title: The cis-acting replication element of the Hepatitis C virus genome recruits host factors that influence viral replication and translation.
abstract: The cis-acting replication element (CRE) of the hepatitis C virus (HCV) RNA genome is a region of conserved sequence and structure at the 3' end of the open reading frame. It participates in a complex and dynamic RNA-RNA interaction network involving, among others, essential functional domains of the 3' untranslated region and the internal ribosome entry site located at the 5' terminus of the viral genome. A proper balance between all these contacts is critical for the control of viral replication and translation, and is likely dependent on host factors. Proteomic analyses identified a collection of proteins from a hepatoma cell line as CRE-interacting candidates. A large fraction of these were RNA-binding proteins sharing highly conserved RNA recognition motifs. The vast majority of these proteins were validated by bioinformatics tools that consider RNA-protein secondary structure. Further characterization of representative proteins indicated that hnRNPA1 and HMGB1 exerted negative effects on viral replication in a subgenomic HCV replication system. Furthermore DDX5 and PARP1 knockdown reduced the HCV IRES activity, suggesting an involvement of these proteins in HCV translation. The identification of all these host factors provides new clues regarding the function of the CRE during viral cycle progression.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, (IPBLN-CSIC). PTS Granada, Avda. del Conocimiento s/n, Armilla, 18016 Granada, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ríos-Marco
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, (IPBLN-CSIC). PTS Granada, Avda. del Conocimiento s/n, Armilla, 18016 Granada, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Romero-López
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, (IPBLN-CSIC). PTS Granada, Avda. del Conocimiento s/n, Armilla, 18016 Granada, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berzal-Herranz
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D063990:Gene Ontology; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D053719:Tandem Mass Spectrometry; D014779:Virus Replication / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins