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

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.