Sequence variability at the internal ribosome entry site of the HCV genome in relation to therapy outcome
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Abstract
Different types of interferon are widely used to treat hepatitis C virus (HCV) infection. Results obtained in vitro suggest that interferon inhibits internal ribosome entry site (IRES)-mediated translation of the HCV genome. To elucidate the possible effect of the nucleotide sequence of IRES on therapy outcome, we compared HCV isolates from patients with sustained response and non-response to interferon/ribavirin combination therapy. In 56 analyzed HCV isolates, nucleotide changes appeared strictly in the stem-loop IIIb region, the stem part from 243 nt to 248 nt, and the polypyrimidine-II region. The natural sequence variability of IRES in isolates of genotype 3a was significantly higher than in isolates of genotype 1b (p < 0.05). The average number of nucleotide changes in genotype 3a correlated with response to therapy (p < 0.05).Interferonska terapija se danas najčešće koristi u lečenju infekcije virusom hepatitisa tipa C (HCV). In vitro rezultati su pokazali da interferoninhibira translaciju kod ovog virusa preko interakcije sa delom genoma koji učestvuje u inicijaciji translacije tzv. 'unutrašnje ribozomalno ulazno mesto' (IRES). U ovom radu smo ispitivali nukleotidne izmene u IRES-u kod izolata HCV-a dobijenih iz seruma osoba koje su primale kombinovanu terapiju interferon/ribavirin. U analiziranoj grupi od 56 HCV izolata, nukleotidne izmene su utvrđene u: IIIb petlji, regiji između 243 nt i 248 nt i polipirimidin-II regiji. Utvrđena varijabilnost IRES-a kod izolata genotipa 3a značajno je veća u poređenju sa izolatima genotipa 1b (p < 0.05). Prosečan broj nukleotidnih izmena kod izolata genotipa 3a je u korelaciji sa odgovorom na primenjenu terapiju (p < 0.05).Projekat ministarstva br. 143010 i 14301