Interferons specifically suppress the translation from the internal ribosome entry site of hepatitis C virus through a double-stranded RNA-activated protein kinase-independent pathway.
Interferon (IFN) therapy is used worldwide as the best available treatment for hepatitis C virus (HCV) infection; however, little is known about how IFN or other drugs work against liver diseases. The effect of 6 drugs (glycyrrhizin, ursodeoxycholic acid, ribavirin, methylprednisolone, IFN-alpha, and IFN-beta) on HCV RNA translation from the HCV internal ribosome entry site (IRES) was investigated, using a bicistronic reporter containing the HCV IRES. IFNs suppressed both cap-dependent and HCV IRES-dependent translation, with HCV IRES-dependent translation being more significantly suppressed. In contrast to HCV IRES, IFN did not suppress either foot-and-mouth disease virus IRES-dependent or encephalomyocarditis virus IRES-dependent translation more than it suppressed cap-dependent translation. Moreover, dominant inhibition of HCV IRES-dependent over cap-dependent translation depended neither on the double-stranded RNA-activated protein kinase activation nor on La protein function. These results indicate a novel antiviral effect of IFNs against HCV.
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Jun
J
Kato
Naoya
N
Kato
Masaru
M
Moriyama
Tadashi
T
Goto
Hiroyoshi
H
Taniguchi
Yasushi
Y
Shiratori
Masao
M
Omata
D000890:Anti-Infective Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D001324:Autoantigens / Q000096:biosynthesis; D015153:Blotting, Western; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004686:Encephalomyocarditis virus / Q000378:metabolism; D029544:Foot-and-Mouth Disease Virus / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000096:biosynthesis; D012270:Ribosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014580:Ursodeoxycholic Acid / Q000494:pharmacology; D000097585:SS-B Antigen
D000890:Anti-Infective Agents; D000998:Antiviral Agents; D001324:Autoantigens; D002756:Cholagogues and Choleretics; D005938:Glucocorticoids; D019695:Glycyrrhizic Acid; D007372:Interferons; D008775:Methylprednisolone; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D012254:Ribavirin; D012261:Ribonucleoproteins; D014580:Ursodeoxycholic Acid; D000097585:SS-B Antigen