...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity
【24h】

Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity

机译：卡波西氏肉瘤相关疱疹病毒K5下调NKG2D和NKp80配体可抵抗NK细胞的细胞毒性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Natural killer (NK) cells are important early mediators of host immunity to viral infections. The NK activatory receptors NKG2D and NKp80, both C-type lectin-like homodimeric receptors, stimulate NK cell cytotoxicity toward target cells. Like other herpes-viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) down-regulates MHC class I molecules to avoid detection by cytotoxic T lymphocytes but renders cells susceptible to NK cell cytotoxicity. We now show that the KSHV immune evasion gene, K5, reduces cell surface expression of the NKG2D ligands MHC class l-related chain A (MICA), MICB, and the newly defined ligand for NKp80, activation-induced C-type lectin (AICL). Down-regulation of both MICA and AICL requires the ubiquitin E3 ligase activity of K5 to target substrate cytoplasmic tail lysine residues. The common MICA ~*008 allele has a frameshift mutation leading to a premature stop codon and is resistant to down-regulation because of the loss of lysine residues. K5-mediated ubiquityla-tion signals internalization but not degradation of MICA and causes a potent reduction in NK cell-mediated cytotoxicity. The down-regulation of ligands for both the NKG2D and NKp80 activation pathways provides KSHV with a powerful mechanism for evasion of NK cell antiviral functions.
机译：天然杀伤（NK）细胞是宿主抵抗病毒感染的重要早期免疫介质。 C型凝集素样同源二聚体受体NK激活受体NKG2D和NKp80刺激NK细胞对靶细胞的细胞毒性。像其他疱疹病毒一样，卡波济氏肉瘤相关疱疹病毒（KSHV）下调MHC I类分子，以避免被细胞毒性T淋巴细胞检测到，但使细胞易受NK细胞的细胞毒性作用。我们现在显示KSHV免疫逃避基因K5减少了NKG2D配体MHC I类相关链A（MICA）和新定义的NKp80配体的细胞表面表达，激活诱导的C型凝集素（AICL ）。 MICA和AICL的下调都需要K5的泛素E3连接酶活性来靶向底物胞质尾赖氨酸残基。常见的MICA〜* 008等位基因具有移码突变，导致终止密码子过早，并且由于赖氨酸残基的丢失而抵抗下调。 K5介导的泛素化信号内化而不是MICA降解，并引起NK细胞介导的细胞毒性的有效降低。 NKG2D和NKp80激活途径的配体的下调为KSHV提供了逃避NK细胞抗病毒功能的强大机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号