cDNA fragments of a 5′-terminal region of the hepatitis C virus (HCV) genome were isolated by the reverse polymerase chain reaction from RNA extracted from plasma samples of healthy Japanese carriers. Their nucleotide sequence was compared with that of the original isolate which had been passaged twice in chimpanzees. No deletions or insertions were observed between the two sequences in the regions examined. Both the 5′ untranslated and putative nucleocapsid (core) protein regions were highly conserved (99% and 91% nucleotide identities, respectively). In contrast, the region immediately downstream which encodes a putative envelope glycoprotein(s) showed only 74% nucleotide identity between the two isolates. At the polypeptide level, the core and envelope domains showed 97% and 75% amino acid identities, respectively. This envelope variation may reflect the adaptation of HCV to the different hosts and/or the result of immunological selection. The highly conserved nucleotide sequence of the 5′ untranslated and core regions may play an important regulatory role in the life cycle of HCV.


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