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.