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Influence of CD8~+ T Cell Pressure on HCV Evolution

Author: GuoYan
Tutor: YangDongLiang
School: Huazhong University of Science and Technology
Course: Internal Medicine
Keywords: CD8~+ T cell immune escape selection pressure CD8 epitope Hepatities C virus(HCV)
CLC: R392
Type: Master's thesis
Year: 2011
Downloads: 28
Quote: 0
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Abstract


. Background:Mutational escape in targeted CD8 epitopes was demonstrated during acute HCV infection. But the influence of CD8~+ T cell pressure on HCV evolution is unknown. some CD8 escape mutations are reproducibly selected in subjects sharing the same restricting HLA-allele. We therefore hypothesize that the HLA-background in a population has an impact on the viral consensus sequence and the frequency of sequence polymorphisms in circulating viruses.. Objective:To study the extent to which this immune adaptation process to vrial evolution at population level.. Methods:We isolated the virus from 69 patient, A nested RT–PCR assay with type specific primers was developed and used for amplification of HCV NS3 region. We identified the mutations according to their location inside or outside previously described CD8 epitopes. Moreover, we identify sites/regions under reproducible HLA–classⅠ-associated selection pressure.. Results:The frequency of mutations was significantly higher inside previously described CD8 epitopes compared to the outside region. Analysis of the 631 amino acids within NS3 revealed 7 amino acid residue(sV1274I/T:95%;Y1444F:68%;T1636I:63%;S1148G:76%;L1382I:75%;S1560G:56%;A1647T:40%) were significantly high, of which 5 amino acid residues(V1274I/T:95%;Y1444F:68%;T1636I:63%;S1148G:76%;L1382I:75%)were inside previously described CD8 epitopes. In some previously described CD8 epitopes mutations were highly reproducible in patients sharing the relevant HLA–allele suggesting reproducible innune pressure at the population level.Conclusion:HLA-classⅠ-associated selection pressure is the major driving force for viral evolution of NS3. A daptation of HCV to CD8~+ T cell immune pressure at the population level further complicates vaccine design.

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