Genetic characterization of hypervariable region 1 in patients chronically infected with hepatitis C virus genotype 2.
The hypervariable region 1 (HVR1) has been most reliably identified in the genome of HCV genotype 1 isolates and thought to possibly play a role in immune evasion and development of chronic infection. There are few studies, however, of other HCV genotypes to determine if they also have such a hypervariable region present, and it is unclear whether or not there is any genotype-dependent difference in the genetic characteristics of HVR1. We determined the nucleotide sequence of 5' end of E2/NS1 region of the HCV genome spanning HVR1 of multiple genotype 1 and 2 HCV isolates and carried out a detailed genetic analysis. Similarity plots identified two hypervariable regions within the genotype 2 sequences, a larger one corresponding to HVR1 as well as a smaller 27-nucleotide region of hypervariability. The synonymous substitutions per synonymous site (ds) was greater than nonsynonymous substitutions per nonsynonymous site (dn) within genotype 1 group whereas dn and ds were similar in the genotype 2 group. Analysis of amino acid sequences revealed several conserved sites across genotype 1 and 2 (amino acid numbers 2,6, 20 and 26) and overall similar hydropathic profiles were found within two genotypes. Still, despite the hypervariability, the HVR1 showed a genotype-specific phylogenetic clustering. Thus, HVR1 appears to be conserved between genotypes in keeping with it having an important survival function. Genotype 2 appears to have a greater rate of nonsynonymous substitutions within HVR1, suggesting a greater positive evolutionary pressure.
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Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Di Bisceglie
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001499:Bayes Theorem; D015331:Cohort Studies; D003198:Computer Simulation; D016384:Consensus Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000821:virology*; D006801:Humans; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D012984:Software