TY - JOUR
T1 - A new role for PGA1 in inhibiting hepatitis C virus-IRES-mediated translation by targeting viral translation factors
AU - Tsukimoto, Atsuko
AU - Sugiyama, Ryuichi
AU - Abe, Makoto
AU - Nishitsuji, Hironori
AU - Shimizu, Yuko
AU - Shimotohno, Kunitada
AU - Kawai, Gota
AU - Takaku, Hiroshi
N1 - Funding Information:
We are grateful to K. Kimizuka for excellent technical assistance. This work was supported by a Grant-in-Aid for HCV Research from the Ministry of Health, Labor, and Welfare of Japan ; a Grant from the Strategic Research Foundation Grant-aided Project for Private Universities from the Ministry of Education, Culture, Sport, Science, and Technology, Japan (MEXT); a Grant-in-Aid for High Technology Research (HTR) from the Ministry of Education, Science, Sports; and a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) (Grant Number 26860309).
PY - 2015/5
Y1 - 2015/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.antiviral.2015.01.013
DO - 10.1016/j.antiviral.2015.01.013
M3 - Article
C2 - 25666760
AN - SCOPUS:84923270639
VL - 117
SP - 1
EP - 9
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -