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首页> 外文期刊>World Journal of Gastroenterology >Sequence evolution of putative cytotoxic T cell epitopes in NS3 region of hepatitis C virus
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Sequence evolution of putative cytotoxic T cell epitopes in NS3 region of hepatitis C virus

机译：丙型肝炎病毒NS3区假定的细胞毒性T细胞表位的序列演变

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AIM: Quasispecies of hepatitis C virus (HCV) are the foundation for rapid sequence evolution of HCV to evade immune surveillance of hosts. The consensus sequence evolution of a segment of HCV NS3 region, which encompasses putative cytotoxic T cell epitopes, was evaluated. METHODS: Three male patients, infected with HCV through multiple transfusions, were identified from clinical symptoms and monitored by aminotransferase for 60 months. Blood samples taken at months 0, 32, and 60 were used for viral RNA extraction. A segment of HCV NS3 region was amplified from the RNA extraction by RT-PCR and subjected to subcloning and sequencing. HLA types of these three patients were determined using complement-dependent microlymphocytotoxic assay. CTL epitopes were predicted using MHC binding motifs. RESULTS: No patient had clinical symptoms or elevation of aspartate/alanine aminotransferase. Two patients showed positive HCV PCR results at ail 3 time points. The other one showed a positive HCV PCR result only at month 0. A reported HLA-A2-restricted CTL epitope had no alteration in the HLA-A2-negative carrier over 60 months. In the HLA-A2-positive individuals, all the sequences from 0 month 0 showed an amber mutation on the initial codon of the epitope. Most changes of consensus sequences in the same patient occurred on predicted cytotoxic T cell epitopes. CONCLUSION: Amber mutation and changes of consensus sequence in HCV NS3 region may be related to viral immune escape.
机译：目的：丙型肝炎病毒（HCV）的准种是HCV快速序列进化以逃避宿主免疫监视的基础。评估了HCV NS3区片段的共有序列进化，该序列涵盖了假定的细胞毒性T细胞表位。方法：从临床症状中识别出三例经多次输血感染HCV的男性患者，并通过氨基转移酶监测60个月。在第0、32和60个月采集的血液样本用于病毒RNA提取。通过RT-PCR从RNA提取中扩增出HCV NS3区域的片段，并进行亚克隆和测序。这三名患者的HLA类型使用补体依赖性微淋巴细胞毒性测定法确定。使用MHC结合基序预测CTL表位。结果：没有患者有临床症状或天冬氨酸/丙氨酸转氨酶升高。两名患者在所有3个时间点均显示HCV PCR阳性结果。另一个仅在第0个月才显示HCV PCR阳性。报告的HLA-A2限制性CTL表位在60个月内未改变HLA-A2阴性载体。在HLA-A2阳性个体中，从0月0日开始的所有序列在表位的初始密码子上显示出琥珀色突变。同一患者中共有序列的大多数变化发生在预测的细胞毒性T细胞表位上。结论：HCV NS3区域的琥珀色突变和共有序列的改变可能与病毒免疫逃逸有关。

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