Sequence variation in hepatitis C viral isolates.

The single stranded, RNA genome of the hepatitis C (HCV) virus was characterized after approximately a decade of research in the field of non-A, non-B hepatitis (NANBH) (1, reviewed in Refs. 2 and 3). Since 1987, three genomes encoding the 3010-3011 amino acid putative precursor polyprotein (4-6) and numerous partial nucleotide sequences have been reported (reviewed in Refs. 7 and 8). Based on a comparison of the sequences available to date, Houghton et al. proposed that there are at least three groups of closely related HCV viruses (7). Of the two groups for which the nearly full-length genome has been determined (I :jk Ir;, KWI~WXS within a group appear to be 92% (95%) identical in the nucleotide (amino acid) sequence; while the overall percent nucleotide (amino acid) homology between groups is 7879% (85%). The range of deduced amino acid sequence homology in specific HCV proteins may be greater or lesser than the average over the entire putative polyprotein. For example, the putative nucleocapsid protein (Fig. 1) appears to be the most highly conserved protein both between members of the same group and between different groups (98-100% and 97-98%, respectively) (Refs. 7, 9 and 10, also see Fig. 2) and has therefore been especially useful for immunological (11-15) and hybridization based diagnostic tests for HCV (16). In contrast, the putative envelope glycoprotein El (gp33) is greater than 90% conserved in the amino acid sequence of isolates within a group but is only approx. 77-81% conserved between groups I and II (reviewed in Ref. 7; also see Fig. 3). The deduced amino acid sequence of the putative NS2 protein appears to be the most heteroge5 3 I I I I