Characterisation of the translation efficiency and quasispecies composition of the 5'untranslated region of Hepatitis C virus in genotype 1 and 3 infected patients

Abstract

Hepatitis C virus (HCV) infects over 170 million people worldwide. Chronic infection occurs in 50-80% of cases and eventually leads to cirrhosis and hepatocellular carcinoma. HCV can be classified into six genotypes. Genotypes 1, 2 and 3 have a world-wide distribution but their prevalence differs from one geographical area to another. In Scotland there is an approximate 50/50 split between patients infected with HCV genotype 1 and genotype 3. One difference which has been consistently demonstrated is the better response of patients infected with genotypes 2 and 3 to interferon treatment than those infected with genotype 1. The HCV lifecycle is only partly understood owing to the lack of a productive cell culture system. There is no vaccine to prevent infection by HCV. Given the predicted future impact of the disease, there is a great need to understand the molecular basis of the HCV life cycle. Protein translation is one of the important processes in HCV replication. It involves an internal ribosome entry site (IRES) in the 5'untranslated region (5'UTR). Comparison of the sequence and function of the 5'UTR from different genotypes might differentiate features essential to the virus life cycle in all genotypes from those relevant only to individual genotypes. In this study, the 5'UTR region of genotype 3 was compared with that of genotype 1 with respect to translation initiation and quasispecies composition. The association between translation efficiencies, serum viral loads and the histology of the liver was also investigated. (Abstract shortened by ProQuest.)