Comparative analysis of translation efficiencies of hepatitis C virus 5 ' untranslated regions among intraindividual quasispecies present in chronic infection: Opposite behaviors depending on cell type

Hepatitis C virus (HCV) RNA translation initiation is dependent on the pres ence of an internal ribosome entry site (IRES) that is found mostly in its 5' untranslated region (5' UTR). While exhibiting the most highly conserved sequence within the genome, the 5' UTR accumulates small differences, whic h may be of biological and clinical importance, In this study, using a bici stronic dual luciferase expression system,,ve have examined the sequence of 5' UTRs from quasispecies characterized in the serum of a patient chronica lly infected with HCV genotype la and its corresponding translational activ ity. Sequence heterogeneity between IRES elements led to important changes in their translation efficiency both in vitro and in different cell culture s lines, implying that interactions of RNA with related transacting factors may vary according to cell type. These data suggest that variants occasion ally carried by the serum prior to reinfection could be selected toward dif ferent compartments of the same infected organism, thus favoring the hypoth esis of HCV multiple tropism.