Classification of hepatitis C virus into subgroups on the basis of sequence variations in the envelope protein

In order to investigate the possibility that hepatitis C virus (HCV) can be classified into subgroups based on the variations in the envelope region, the nucleotide and deduced amino acid sequences were compared among the reported viral isolates including HCV1, HCJ1, HCJ4, HCVJ, HCVBK, HCVNK and HCJ6. From the homology analysis, the HCV isolates were classified into three subgroups: group I (HCV1 and HCJ1); group II (HCJ4, HCVJ, HCVBK and HCVNK); and group III (HCJ6). Furthermore, two novel regions were found in the E1 envelope region. One is located at aa246–258 (intersubtype variable region 1; ISVR-1) where the amino acid sequences were relatively conserved within each subgroup, while the sequences were extremely different among the subgroups. Another is located at aa315–328 (intersubgroup common region-1; ISCR-1) where the amino acid sequences were completely identical among all seven HCV isolates despite the fact that the marked variations were distributed throughout the envelope region. The results suggest that the combination of ISVR-1 and ISCR-1 can be utilized as marker sequences for the classification of HCV strains and that the letter region might be one of the candidates for the vaccine.