Analysis of Variation of Hepatitis C Viral Genome.

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The genome of Japanese hepatitis C virus (HCV-J), causative agent of C-type hepatitis, has analyzed using the information of patent of Chiron Corp. containing a part of the genome structure of HCV. We have determined the nucleotide sequence of whole genomic structure of HCV-J from cDNA clones which were obtained by the amplification with RT-PCR and screening of cDNA library. HCV-J genome was 9422 nucleotides in length and had a long open reading frame of 9030 nucleotides. At the amino acid level we could find weak homology with those of the Flaviviridae, but not find any significant homology of the nucleotide sequence with other animal viruses. Therefore, we concluded that HCV-J should be classified into a new virus family distinct from the flaviviruses and pestiviruses. Comparison of HCV-J with the original isolate of HCV (HCV-US) showed 24% difference in nucleotide sequence and 15% difference in amino acid sequence and we proposed that HCV-J and HCV-US are different subtype HCV.We ha … More ve also analyzed the nucleotide sequence of putative NS5 region, which encodes RNA polymerase, by RT-PCR. 19 HCV-J genomes were obtained from 16 specimens (serum of patients with hepatitis and hepatocellular carcinoma) in various areas of Japan. 14-17% of nucleotide sequence in this region was different from that of HCV-US. Furthermore, 2.5-11% of nucleotide sequence and 0-7% of amino acid sequence differed among HCV-J genomes. These results showed the heterogeneity and variation of the genomes. HCV-US types were found in Japanese hemophiliacs received imported blood products and sequence diversity (2-8% of nucleotide sequence) was found among HCV-US types. Sequence diversity of putative envelope region was also analyzed as well as RNA polymerase domain. Variation of this region was more remarkable and 12-31% of amino acid sequence differed among virus strains. Notably, we found two hypervariable regions, however, we gave to clarify the relationship between these variable regions and the mechanism of persistent infection of virus, in future. Less