Secondary structure of the hepatitis C virus 5' untranslated region and efficacy of interferon therapy for chronic hepatitis C.

Abstract

The hepatitis C virus 5' untranslated region (HCV 5'UTR) contains secondary structures typical of internal ribosome entry site elements leading to translation. Variations of this secondary structure in relation to the efficacy of interferon (IFN) therapy were investigated. Natural IFN-alpha was administered to 22 patients with chronic hepatitis C due to HCV subtype 1b and their serum HCV-RNA levels were examined using the reverse-transcription polymerase chain reaction (RT-PCR). The HCV 5'UTR sequence was determined by direct sequencing, and variations of the putative secondary structure were detected by analyzing single-strand confirmation polymorphisms (SSCP) in the patient's sera. Five of the 22 patients (22%) were complete responders to IFN and eradicated HCV-RNA from their sera and 17/22 (78%) were nonresponders in whom HCV-RNA persisted. The SSCP electrophoretic results predicted the efficacy of IFN therapy: the complete responders showed greater pattern diversity than the nonresponders. The serum HCV-RNA level correlated with the SSCP electrophoretic pattern: patients with the IFN-resistant SSCP electrophoretic pattern had higher levels than the others (10.1+/-2.4 vs 1.2+/-0.4 Meq/ml; p<0.001). Sequencing analysis suggested three one-point mutations influence alteration of the secondary structure. Analysis of the secondary structure of the HCV 5'UTR contributes to predicting viremia severity and the efficacy of IFN therapy in patients with chronic hepatitis C.