The 5'-terminal sequence of the genome of hepatitis C virus (HCV) was determined for two distinct HCV strains in human and chimpanzee carriers. It had a 5'-noncoding region of at least 324 nucleotides, well preserved by the two strains with a high homology (99.1%), followed by 1348 nucleotides that continued to the documented sequence of prototype HCV spanning 7310 nucleotides (European Patent Application #88310922.5). Based on these results, HCV is considered to possess an uninterrupted open reading frame encoding at least 2886 amino acid residues. Two structural genes were postulated on the 5'-terminal sequence of the HCV genome. One gene in the upstream region, highly conserved by the two strains at the amino acid level and rich in basic amino acids such as arginine, appeared to encode the viral capsid protein. The other gene in the downstream region was divergent between the two strains at both nucleotide and amino acid levels. It coded for nine potential N-glycosylation sites, and was considered to encode the viral envelope protein. Disclosure of the 5'-terminal sequence of the HCV genome would facilitate its taxonomic classification, and contribute toward immunological diagnosis of infection and development of vaccines.
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