Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes.

Variable genomic sequences have been reported for RNA cloned from hepatitis C virus (HCV)-infected humans and chimpanzees. We found that four distinct genotypes of HCV could be differentially identified by PCR using type-specific primers. Full-length sequences have so far been reported for three of the four HCV genotypes, and we report herewith the sequence of the fourth type obtained from a Japanese blood donor. The entire nucleotide sequence of the HCV isolate (HC-J8) comprised 9481 bases plus a 3'-terminal poly(U) stretch of variable length. Like all previous isolates, the RNA contained a single, long open reading frame for a polyprotein of 3033 amino acids. HC-J8 differed from previously reported HCV isolates by 23.1-33.1% in nucleotide sequence and 15.9-28.8% in amino acid sequence. Based on genomic sequence homologies, a proposed phylogenetic tree of HCV, with a fourth branch represented by HC-J8, allowed a classification of all HCV isolates whose complete or partial sequences are now known. This classification suggests that all or most HCV genome sequences will fall into one of the proposed four types. The classification may be helpful in designing vaccine studies and for serological investigations of possible group- and type-specific antibodies.