title: Human eukaryotic initiation factor 4AII associates with hepatitis C virus NS5B protein in vitro.
abstract: Hepatitis C virus (HCV) NS5B protein has been shown to have RNA-dependent RNA polymerase (RdRp) activity by itself and is a key enzyme involved in viral replication. Using analyses with the yeast two-hybrid system and in vitro binding assay, we found that human eukaryotic initiation factor 4AII (heIF4AII), which is a component of the eIF4F complex and RNA-dependent ATPase/helicase, interacted with NS5B protein. These two proteins were shown to be partially colocalized in the perinuclear region. The binding site in HCV NS5B protein was localized within amino acid residues 495 to 537 near the C terminus. Since eIF4A has a helicase activity and functions in a bidirectional manner, the binding of HCV NS5B protein to heIF4AII raises the possibility that heIF4AII facilitates the genomic RNA synthesis of NS5B protein by unwinding the secondary structure of the HCV genome and is a host component of viral replication complex.
authors.affiliation: Discovery Research Laboratory, Tanabe Seiyaku Company, Ltd., 16-89 Kashima 3-chome, Yodogawa-ku, Osaka 532-8505, Japan. k-kyono@tanabe.co.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kyono
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miyashiro
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Taguchi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D039601:Eukaryotic Initiation Factor-4A; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010448:Peptide Initiation Factors; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; D039601:Eukaryotic Initiation Factor-4A; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase