title: A new role for PGA1 in inhibiting hepatitis C virus-IRES-mediated translation by targeting viral translation factors.
abstract: Previous studies have demonstrated that cyclopentenone prostaglandins (cyPGs) inhibit the replication of a wide variety of DNA and RNA viruses in different mammalian cell types. We investigated a new role for prostaglandin A1 (PGA1) in the inhibition of hepatitis C virus (HCV)-IRES-mediated translation. PGA1 exhibited dose-dependent inhibitory effects on HCV translation in HCV replicon cells. Furthermore, repetitive PGA1 treatment demonstrated the potential to safely induce the suppression of HCV translation. We also validated a new role for PGA1 in the inhibition of HCV-IRES-mediated translation by targeting cellular translation factors, including the small ribosomal subunit (40S) and eukaryotic initiation factors (eIFs). In pull-down assays, biotinylated PGA1 co-precipitated with the entire HCV IRES RNA/eIF3-40S subunit complex. Moreover, the interactions between PGA1 and the elongation factors and ribosomal subunit were dependent upon HCV IRES RNA binding, and the PGA1/HCV IRES RNA/eIF3-40S subunit complex inhibited HCV-IRES-mediated translation. The novel mechanism revealed in this study may aid in the search for more effective anti-HCV drugs.
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors: Atsuko
authors: A
authors: Tsukimoto
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors: Ryuichi
authors: R
authors: Sugiyama
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors: Makoto
authors: M
authors: Abe
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kounodai, Ichikawa, Chiba 272-8516, Japan.
authors: Hironori
authors: H
authors: Nishitsuji
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kounodai, Ichikawa, Chiba 272-8516, Japan.
authors: Yuko
authors: Y
authors: Shimizu
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kounodai, Ichikawa, Chiba 272-8516, Japan.
authors: Kunitada
authors: K
authors: Shimotohno
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
authors: Gota
authors: G
authors: Kawai
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; High Technology Research Center, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan; Research Institute, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan. Electronic address: hiroshi.takaku@p.chibakoudai.jp.
authors: Hiroshi
authors: H
authors: Takaku
mesh_terms: D045744:Cell Line, Tumor; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism*; D006801:Humans; D000067556:Internal Ribosome Entry Sites; D011454:Prostaglandins A / Q000378:metabolism* / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012367:RNA, Viral / Q000235:genetics; D012093:Replicon / Q000187:drug effects* / Q000502:physiology; D054679:Ribosome Subunits, Small / Q000187:drug effects* / Q000378:metabolism
chemical_list: D039621:Eukaryotic Initiation Factor-3; D000067556:Internal Ribosome Entry Sites; D011454:Prostaglandins A; D012367:RNA, Viral; C100573:prostaglandin A1
keywords: Eukaryotic initiation factors eIF3; HCV; HCV IRES RNA; Prostaglandin A(1); Small ribosomal subunit (40S); Translation inhibition