Inhibition of hepatitis C virus IRES-mediated translation by oligonucleotides.
Two oligodeoxynucleotides (ODNs) were found to have a strong inhibition on the hepatitis C virus (HCV) internal ribosomal entry sites (IRES)-mediated translation but not the rabbit globin mRNA translation. Specific inhibition of those ODNs on HCV IRES-mediated translation was confirmed with heat treatment of ODNs in formic acid and dosage-dependent manners. Heat treatment of ODNs presented a decreasing inhibitory effect on HCV IRES-mediated translation. A dosage-dependent decrease of HCV IRES-mediated translation was observed with increasing amount of these ODNs in HeLa cell extracts. The minimal sequences of ODNs (A11) were identified as 5'-CGCGTTACG-3' with the strongest inhibition of the HCV IRES-mediated translation. In a search for cellular factors, two cellular factors (p68 and p70) were identified to interact with ODNs A1 and A11, but not A5 (CT-oligo). This data showed new kinds of cellular proteins involved in HCV IRES-mediated translation. Further study of ODNs and these cellular proteins will provide important information for understanding the mechanistic basis and molecular regulation of HCV IRES-mediated translation.
Li
Xiaoyu
X
Division of Gastroenterology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, FL 32206, United States. xiaoyu.li@jax.ufl.edu
Mueller
Steffen
S
Wimmer
Eckard
E
D000998:Antiviral Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D016174:Hepacivirus / Q000187:drug effects*; D054884:Host-Pathogen Interactions; D006801:Humans; D009841:Oligonucleotides / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*
D000998:Antiviral Agents; D009841:Oligonucleotides