Escape mutations alter proteasome processing of major histocompatibility complex class I-restricted epitopes in persistent hepatitis C virus infection
Escape mutations alter proteasome processing of major histocompatibility complex class I-restricted epitopes in persistent hepatitis C virus infection
复制标题
DOI：
10.1128/jvi.79.8.4870-4876.2005
复制
发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Walker, CM
中科院分区：
文献类型：
--
作者：
Kimura, Y;Gushima, T;Walker, CM
丙型肝炎病毒（HCV）基因组的突变有助于持续感染黑猩猩逃避病毒特异性CD8（+）T淋巴细胞。我们以前的研究表明，HCV表位中的许多氨基酸取代阻止了T细胞受体识别或结合I类主要组织相容性复合体分子。在这里，我们报告说，HCV表位内的突变也导致其破坏改变蛋白酶体消化的模式。这种免疫逃避机制为CD8（+）T细胞选择压力对HCV的效力提供了进一步的证据，在评估持续感染黑猩猩和人类的病毒基因组突变的意义时应予以考虑。
Mutations in hepatitis C virus (HCV) genomes facilitate escape from virus-specific CD8(+) T lymphocytes in persistently infected chimpanzees. Our previous studies demonstrated that many of the amino acid substitutions in HCV epitopes prevented T-cell receptor recognition or binding to class I major histocompatibility complex molecules. Here we report that mutations within HCV epitopes also cause their destruction by changing the pattern of proteasome digestion. This mechanism of immune evasion provides further evidence of the potency of CD8(+) T-cell selection pressure against HCV and should be considered when evaluating the significance of mutations in viral genomes from persistently infected chimpanzees and humans.