IN-VIVO TRANSLATIONAL EFFICIENCY OF DIFFERENT HEPATITIS-C VIRUS 5'-UTRS

Initiation of translation in hepatitis C virus (HCV) is dependent on t he presence of an internal ribosome entry site (IRES) contained in its 341-nt-long 5'-untranslated region (UTR), This region is very conserv ed among different isolates and has been used to classify HCV isolates in six different genotypes, These genotypes differ in nucleotide sequ ence that generally preserve the IRES structure, However, the small di fferences seen may be biologically and clinically significant as the H CV strains seem to differ from each other in several important ways, s uch as the behaviour of the viral infection and the response to interf eron therapy, Therefore, differences in translational initiation effic iency amongst the various genotypes could provide an explanation for t hese phenomena, Using a bicistronic expression system we have compared the in vivo translational ability of the three most common European g enotypes of HCV (1, 2, and 3), The results show that genotype 3 is les s able than 1 and 2 to promote translation initiation, In addition, by site-directed mutagenesis of the sequence of the IRES domain III apic al stem loop structure, we have shown that the conservation of the pri mary nucleotide sequence and not only the structure, is important for the conservation of IRES function. (C) 1997 Federation of European Bio chemical Societies.