HETEROGENEITY OF HEPATITIS-C VIRUS GENOTYPES IN FRANCE

The genotypes of French hepatitis C virus (HCV) isolates were investig ated by amplification of a domain from the non-structural region 3 (NS 3) using nested PCR, followed by hybridization with two genotype-speci fic probes, F1 (HCV type I-specific) and F2 (HCV type II-specific). Am ong 119 HCV RNA-positive sera, 91% of samples were NS3 PCR positive. M ost samples (83.2%) hybridized with one or the other probe only, where as a few samples (4.2%) hybridized with both F1 and F2 probes (HB). A small percentage (3.4%) of samples appeared unable to hybridize with e ither probe (HN). For some of these samples (HB1, HB2, HN1, HN2, HN3, HN4), part of the NS3, core and envelope regions were sequenced and th e corresponding deduced consensus sequences were compared with those o f prototype isolates of the four HCV genotypes (types I to IV). A phyl ogenetic tree was constructed to illustrate the relationship between t hese isolates. The results obtained showed that (i) KN4 appears to be more closely related to type III than to type IV HCV genotypes, which suggests that in France there may exist additional although minor geno types besides the two major types, F1 and F2. (ii) HB1, HB2, HN1, HN2 and probably HN3 belong to the type II HCV genotype. The association b etween sequence diversity and putative biological difference for isola tes within the same geno-type remains to be elucidated.