A new role for PGA1 in inhibiting hepatitis C virus-IRES-mediated translation by targeting viral translation factors

Atsuko Tsukimoto, Ryuichi Sugiyama, Makoto Abe, Hironori Nishitsuji, Yuko Shimizu, Kunitada Shimotohno, Gota Kawai, Hiroshi Takaku

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalAntiviral Research
Volume117
DOIs
Publication statusPublished - 05-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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