The entire nucleotide sequence of genomic DNA was determined for hepatitis B virus (HBV) of subtype , which had been derived from the blood of a Japanese asymptomatic carrier. The genome was 3215 nucleotides long, and differed in DNA sequence by 10% from that of subtypes or , but by only 2% from that of subtype . Amino acid sequences coded for by the S, C, P and X genes, as well as by the pre-S region, closely resembled those of subtype , indicating that the evolution of HBV/ from HBV/ was more recent than the differentiation of the other three subtypes. In the product of the S gene, the mutually exclusive subtypic determinants of the surface antigen, and , were associated with variation of amino acid residues at only the 68th and 122nd positions from the N terminus, in contrast to the variation at as many as seven positions for the other set of subtypic determinants, and . Sequences representing high local hydrophilicity in the product of the S gene were involved in subtypic variation, although such sequences in the pre-S region were shared by HBV genomes of the various subtypes. In particular, a hydrophilic sequence of 19 amino acid residues, coded for by the pre-S(2) region and implicated in the presumed hepatotropism of HBV, was possessed in common by HBV/, HBV/ and HBV/, and differed in HBV/ by only one residue at the 9th position. This amino acid sequence appears to be a promising candidate for a synthetic peptide vaccine.


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