Hepatitis C virus genotype 6 currently contains 21 recognized subtypes, 6a-6u, for which 6r and 6s lack complete genome sequences. In this study, we entirely sequenced variants QC245 and QC66 from Cambodian immigrants in Canada representing subtypes 6r and 6s, respectively. The two genomes shared 75.3% nucleotide similarities to each other and 72.0-82.9% to 21 reference sequences representing subtypes 6a-6q, 6t-6u and variants km41 and gz52557. QC66 and QC245 displayed genome lengths of 9473 and 9450 nt and each contained a single open reading frame of 9051 nt. In 10 protein encoding regions QC245 and QC66 shared common sizes with TV249/6t and 537796/6l isolates, respectively. Phylogenetic analyses demonstrated that QC245 was more closely related to subtype 6f, but both QC66 and QC245 were subtypically different from all other genotype 6 subtypes. Our full-length sequence data confirmed the status of subtype 6r and 6s within genotype 6. Analysis of partial sequences revealed seven 6t and two 6s isolates that were all isolated from Cambodian immigrants. Analysis of the hypervariable region 1 sequences of 81 genotype 6 variants revealed two unique patterns of variation. First, most variants showed an amino acid deletion at the 4th position and second, many contained a basic residue at the 7th position. Possible roles of these two variation patterns are further discussed.
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