Journal
JOURNAL OF MOLECULAR EVOLUTION
Volume 54, Issue 4, Pages 465-473Publisher
SPRINGER-VERLAG
DOI: 10.1007/s00239-001-0037-6
Keywords
HCV-NS3; chronic hepatitis C; sequencing; escape variant; positive selection
Funding
- NHLBI NIH HHS [P01-HL44612] Funding Source: Medline
- NIAID NIH HHS [R01-AI47347] Funding Source: Medline
- NIDDK NIH HHS [R01-DK57732, K01-DK02970] Funding Source: Medline
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To determine whether the persistent nature of hepatitis C infection is related to the emergence of antigenic variants driven by immune selection, we examined the sequence heterogeneity in a portion of the hepatitis C virus (HCV) nonstructural 3 (NS3) gene of a patient infected over the course of more than 2 years. By PCR amplification, cloning, and sequencing, we observed several variable and conserved regions in the NS3 segment of the HCV genome. All variable regions had higher ratios of nonsynonymous/synonymous mutations and encompassed immunodominant epitopes, and their locations were not essential to maintain the known function of HCV RNA helicase. In contrast, the regions that are critical for HCV RNA helicase activity were found to be conserved with lower heterogeneity or lower ratios of nonsynonymous/synonymous mutations, and none except one of these regions was encoded within immunodominant epitopes. Our results are consistent with immune selection of viral variants at the epitope and molecular levels that may enable HCV to evade host defenses over time. Plotting the relatedness of sequence variants revealed a star topology suggesting that a wildtype HCV sequence is maintained, unlike HIV.
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