2008
DOI: 10.1128/jvi.01700-07
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Analysis of the Evolutionary Forces in an Immunodominant CD8 Epitope in Hepatitis C Virus at a Population Level

Abstract: Failure of the adaptive immune response to control infection with the hepatitis C virus (HCV) can result from mutational escape in targeted T-cell epitopes. Recent studies suggest that T-cell immune pressure is an important factor in the evolution of the nonstructural proteins in HCV. The aim of this study was to characterize the forces that contribute to viral evolution in an HLA-A*01-restricted epitope in HCV NS3. This epitope represents a potentially attractive target for vaccination strategies since it is … Show more

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Cited by 58 publications
(61 citation statements)
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“…25 However, more than one polymorphism was present in most HLA-B*2705-positive genotype 1-infected individuals, in line with the previous observation that clustered mutations outside the anchor position are required for efficient escape. 25 In contrast, a single mutation at position 9 appears sufficient to abrogate T cell responses in the A*0101-restricted NS3-1436 epitope 8 (Fig. 2).…”
Section: Discussionmentioning
confidence: 95%
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“…25 However, more than one polymorphism was present in most HLA-B*2705-positive genotype 1-infected individuals, in line with the previous observation that clustered mutations outside the anchor position are required for efficient escape. 25 In contrast, a single mutation at position 9 appears sufficient to abrogate T cell responses in the A*0101-restricted NS3-1436 epitope 8 (Fig. 2).…”
Section: Discussionmentioning
confidence: 95%
“…The two adaptation sites that overlap between the genotypes were found in areas of conservation, and one falls within an HLA-A1-restricted epitope that has recently been shown to induce CTL responses in individuals infected with genotypes 1 and 3. 8 Cross-genotype epitopes are likely to occur in predominantly conserved areas with similar consensus sequence. These results may provide some explanation as to the relative lack of cross-protection between genotypes in HCV-infected individuals 29,30 and may be relevant to the difference in the response rates to immunomodulatory-based therapy with interferon-␣ and ribavirin.…”
Section: Discussionmentioning
confidence: 99%
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“…Natural variants of an immunodominant, HLA-B*0801-restricted CD8 + T cell Ag, 1395 HSKKKCDEL 1403 (HSK), derived from the highly immunogenic HCV nonstructural protein 3, have been reported previously (9)(10)(11). HLA-B*0801 is a common allele, prevalent in 10-18% of Caucasian populations (5).…”
mentioning
confidence: 99%