VARIATION OF THE HEPATITIS-C VIRUS 5' NONCODING REGION - IMPLICATIONSFOR SECONDARY STRUCTURE, VIRUS DETECTION AND TYPING

Variation in the 5' non-coding region (5'NCR) of hepatitis C virus (HC V) was investigated in detail by comparing 314 5'NCR sequences of viru ses of genotypes 1 to 6. Evidence was obtained for the existence of as sociations between particular 5'NCR sequence moths and virus types and subtypes. No recombination was observed between the 5'NCR and coding regions of different genotypes, implying that the sequence of subgenom ic regions such as the 5'NCR can be used to deduce virus genotype. The distribution of polymorphic sites within the 5'NCR is used to propose improved oligonucleotide primers for virus detection and quantificati on that would be equally efficient in detecting RNA of different virus genotypes. The accuracy of two different genotyping methods (RFLP and the line probe assay) based on analysis of sequence polymorphisms in the 5'NCR is predicted from the sequences surveyed to be 97% and 83% r espectively for types 1 to 6, with higher accuracies for distinguishin g between subtypes 1a/1b, 2a/2b or 3a/3b. Several sites of genotype-sp ecific polymorphism were covariant and maintained the base pairings re quired for a secondary structure model of the 5'NCR. Other sites of va riation suggest minor modifications to this model and have implication s for the probable functions of the 5'NCR