Four distinct genotypes of hepatitis C virus types I, 11, 1 1 1 and IV have been identified by comparison of nucleotide sequences of isolates from different areas of the world. W e examined the possibility that hepatitis C virus may have serologically defhable subtypes. Enzyme-linked immunosorbent assay systems were prepared by use of two synthetic peptides deduced from the putative core protein of hepatitis C virus.
The following are the two peptides that were used: (a) IPgARRPEGFNPGY (subtype-1) conserved in hepatitis C virus isolates with type I and type 1 1 genotypes; and (b) IPgDRRS'JGBWGJPGY (subtype-2) conserved in type III and type IV genotypes. With the enzyme-linked immunosorbent assays, the subtype-1 antibodies were detected in 26 (68%) of 38 subjects whose hepatitis C virus RNA had been genotyped as type I or type 11, whereas subtype-2 antibodies were not detected. Inversely, the subtype-2 antibodies were detected in 10 (56%) of 18 subjects with hepatitis C virus RNA genotypes 1 1 1 or IV, whereas subtype-1 antibodies were detected in none of them. These results suggest that hepatitis C virus has two serologically distinguishable core antigen subtypes, corresponding to either genotype I/II or genotype IIW. Subtyping of HCV by serological methods would contribute to tracking transmission routes of the virus, especially in cases where serum samples were not stored under conditions to preserve RNA or in infected hosts who have cleared the virus and therefore have only antibodies remaining to identify the infection. (HEPATOLOGY 1992; 16886-891.) Within the first few years since Choo et al. described hepatitis C virus (HCV) as a major cause of non-A, non-B hepatitis, numerous other isolates of the virus have been sequenced. They include isolates from different areas of the world, and it is now evident by sequence comparison that HCV has considerable sequence diversity. Okamoto et al. (2, 3) found that all