Cutting Edge: T Cells Monitor N-Myristoylation of the Nef Protein in Simian Immunodeficiency Virus-Infected Monkeys
Cutting Edge: T Cells Monitor N-Myristoylation of the Nef Protein in Simian Immunodeficiency Virus-Infected Monkeys
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DOI：
10.4049/jimmunol.1101216
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发表时间：
2011-07-15
影响因子：
4.4
通讯作者：
Sugita, Masahiko
中科院分区：
文献类型：
--
作者：
Morita, Daisuke;Igarashi, Tatsuhiko;Sugita, Masahiko
利用宿主细胞机制是致病性病毒在宿主细胞中复制的必要条件。HIV和SIV利用宿主衍生的n -肉豆蔻酰基转移酶及其底物肉豆蔻酰基辅酶a，将饱和的C（14）脂肪酸（肉豆蔻酸）偶联到Nef蛋白的n端甘氨酸残基上。这种生化反应被称为n -肉豆蔻酰基化，有助于其靶向质膜，从而支持Nef蛋白的免疫抑制活性。在这项研究中，我们发现宿主免疫系统配备了能够感知Nef蛋白n -肉豆蔻酰化的ctl。建立了恒河猴CD8(+) T细胞系，该细胞系特异性识别n -肉豆芽酰基化而非未经修饰的Nef蛋白肽。此外，在siv感染的猴子循环中发现n -肉豆醇化Nef肽特异性T细胞的种群大小显着增加。因此，这些结果确定n -肉豆蔻酰基化病毒肽是一类新的CTL靶Ag。中华免疫学杂志，2011,18(7):618 -612。
The use of the host cellular machinery is essential for pathogenic viruses to replicate in host cells. HIV and SIV borrow the host-derived N-myristoyl-transferase and its substrate, myristoyl-CoA, for coupling a saturated C(14) fatty acid (myristic acid) to the N-terminal glycine residue of the Nef protein. This biochemical reaction, referred to as N-myristoylation, assists its targeting to the plasma membrane, thereby supporting the immunosuppressive activity proposed for the Nef protein. In this study, we show that the host immunity is equipped with CTLs capable of sensing N-myristoylation of the Nef protein. A rhesus macaque CD8(+) T cell line was established that specifically recognized N-myristoylated, but not unmodified, peptides of the Nef protein. Furthermore, the population size of N-myristoylated Nef peptide-specific T cells was found to increase significantly in the circulation of SIV-infected monkeys. Thus, these results identify N-myristoylated viral peptides as a novel class of CTL target Ag. The Journal of Immunology, 2011, 187: 608-612.