The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes
The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes
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DOI：
10.1016/s1074-7613(01)00245-x
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发表时间：
2001-12-01
期刊：
影响因子：
32.4
通讯作者：
Walker, CM
中科院分区：
文献类型：
--
作者：
Erickson, AL;Kimura, Y;Walker, CM
CD8（+）细胞毒性T淋巴细胞（CTL）被认为可以控制丙型肝炎病毒（HCV）的复制，因此我们研究了为什么这种反应在持续感染的个体中失败。三只持续感染的黑猩猩中的 HCV 准种获得了多个表位突变，从而损害了 I 类 MHC 结合和/或 CTL 识别。大多数逃逸突变出现在急性感染期间，并在准种中保持固定多年，没有进一步多样化。与 HCV 蛋白的邻近区域相比，在表位中观察到氨基酸替代率有统计学上显着的增加。相比之下，当丙型肝炎自发消退时，大多数表位是完整的。我们得出的结论是，CTIL 对 HCV 准种施加正选择压力，并且感染的结果是通过 I 类 MHC 限制性表位的突变来预测的。
CD8(+) cytotoxic T lymphocytes (CTL) are thought to control hepatitis C virus (HCV) replication and so we investigated why this response fails in persistently infected individuals. The HCV quasispecies in three persistently infected chimpanzees acquired mutations in multiple epitopes that impaired class I MHC binding and/or CTL recognition. Most escape mutations appeared during acute infection and remained fixed in the quasispecies for years without further diversification. A statistically significant increase in the amino acid replacement rate was observed in epitopes versus adjacent regions of HCV proteins. In contrast, most epitopes were intact when hepatitis C resolved spontaneously. We conclude that CTIL exert positive selection pressure against the HCV quasispecies and the outcome of infection is predicted by mutations in class I MHC restricted epitopes.