Internal initiation of translation efficiency in different hepatitis C genotypes isolated from interferon treated patients

Initiation of translation of hepatitis C viral RNA occurs internally and it is mediated by a segment of about 330 nucleotides termed Internal Ribosome Entry Site (IRES) located in the 5' end region. While being the most conse rved part of the genome, this region also accumulates nucleotide substituti ons which are often covariant. In this study we have examined the activity and sequence variation of IRES elements belonging to genotypes 1b, 2a/2c an d 3a in patients that responded or not to interferon therapy. The substitut ions found in the IRES region analyzed were predicted to maintain the secon dary structure of the RNA. Comparison of their efficiency to promote intern al initiation of translation in bicistronic constructs supported the conclu sion that for both Ib and 3a genotypes, response to interferon therapy and IRES activity are unrelated, although sequence homology was not always foun d among isolates from patients with different type of response. IRES activi ty of the studied genotypes varied about 4-fold under the conditions used i n our in vivo assays depending on the cell line used for transfection. Such differences were not evidenced in vitro suggesting that the differences ob served depend on trans-acting factors present in the transfected cell.