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

Antiviral research 2015 May

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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. Copyright © 2015 Elsevier B.V. All rights reserved.

Citation

Atsuko Tsukimoto, Ryuichi Sugiyama, Makoto Abe, Hironori Nishitsuji, Yuko Shimizu, Kunitada Shimotohno, Gota Kawai, Hiroshi Takaku. A new role for PGA1 in inhibiting hepatitis C virus-IRES-mediated translation by targeting viral translation factors. Antiviral research. 2015 May;117:1-9