Molecular cloning of an Australian isolate of hepatitis C virus

The genomic sequence of an Australian isolate of hepatitis C virus (HCV) was determined from overlapping cDNA clones obtained from a small amount (1.2 ml) of serum from a single individual with hepatitis C. The isolate (HCV-A) comprises 9379 nucleotides (nt) including 324 nt of a 5' untranslated region (5'UTR), a single long open reading frame of 9033 nt encoding a polyprotein of 3010 amino acids (aa), and 22 nt of a 3' untranslated region (3'UTR). Sequence analysis of a 251 nt region within the 5'UTR and a 222 nt region within NS5B showed the genotype of HCV-A to be subtype 1b. A striking difference in the amino acid sequence of the hypervariable region 1 (HVR-1), and not in the surrounding sequence, was seen in cDNA clones synthesised from serum taken 52 weeks after the initial sample, indicating a significant population diversity of HCV genomes.