title: Amino acids 1-20 of the hepatitis C virus (HCV) core protein specifically inhibit HCV IRES-dependent translation in HepG2 cells, and inhibit both HCV IRES- and cap-dependent translation in HuH7 and CV-1 cells.
abstract: A self-modulating mechanism by the hepatitis C virus (HCV) core protein has been suggested to influence the level of HCV replication, but current data on this subject are contradictory. We examined the effect of wild-type and mutated core protein on HCV IRES- and cap-dependent translation. The wild-type core protein was shown to inhibit both IRES- and cap-dependent translation in an in vitro system. This effect was duplicated in a dose-dependent manner with a synthetic peptide representing amino acids 1-20 of the HCV core protein. This peptide was able to bind to the HCV IRES as shown by a mobility shift assay. In contrast, a peptide derived from the hepatitis B virus (HBV) core protein that contained a similar proportion of basic residues was unable to inhibit translation or bind the HCV IRES. A recombinant vaccinia-HCV core virus was used to examine the effect of the HCV core protein on HCV IRES-dependent translation in cells and this was compared with the effects of an HBV core-recombinant vaccinia virus. In CV-1 and HuH7 cells, the HCV core protein inhibited translation directed by the IRES elements of HCV, encephalomyocarditis virus and classical swine fever virus as well as cap-dependent translation, whereas in HepG2 cells, only HCV IRES-dependent translation was affected. Thus, the ability of the HCV core protein to selectively inhibit HCV IRES-dependent translation is cell-specific. N-terminal truncated (aa 1-20) HCV core protein that was expressed from a novel recombinant vaccinia virus in cells abrogated the inhibitory phenotype of the core protein in vivo, consistent with the above in vitro data.
authors.affiliation: Clinical Medical Virology Research Centre, University of Queensland, St Lucia, QLD 4067, Australia.|Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, QLD 4029, Australia.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: Clinical Medical Virology Research Centre, University of Queensland, St Lucia, QLD 4067, Australia.|Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, QLD 4029, Australia.
authors.forename: Seyed Taghi
authors.initials: ST
authors.lastname: Takyar
authors.affiliation: Clinical Medical Virology Research Centre, University of Queensland, St Lucia, QLD 4067, Australia.|Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, QLD 4029, Australia.
authors.forename: William B
authors.initials: WB
authors.lastname: Lott
authors.affiliation: Clinical Medical Virology Research Centre, University of Queensland, St Lucia, QLD 4067, Australia.|Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, QLD 4029, Australia.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gowans
mesh_terms: D020121:5' Untranslated Regions / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000187:drug effects*; D039381:RNA Cap-Binding Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014779:Virus Replication
chemical_list: D020121:5' Untranslated Regions; D010455:Peptides; D039381:RNA Cap-Binding Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus