Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
复制标题
DOI：
10.1038/nm0396-338
复制
发表时间：
1996-03-01
期刊：
影响因子：
82.9
通讯作者：
Heard, JM
中科院分区：
文献类型：
--
作者：
Schwartz, O;Marechal, V;Heard, JM
与其他致病性病毒一样，HIV-1下调感染细胞中主要组织相容性复合体I类（MHC-I）分子的表面表达，从而损害细胞毒性T淋巴细胞的裂解（1,2）。我们观察到这种现象取决于Nef的表达。nef是灵长类慢病毒的早期基因(3)，它是维持高病毒载量和诱发艾滋病所必需的（参考文献4）。Nef不是体外病毒复制所必需的，它能刺激CD4的内吞作用（参考文献5-8）。我们发现，在各种HIV-1毒株的Nef蛋白存在下，淋巴细胞、单核细胞和上皮细胞表面的MHC-I表达降低。在Nef（+）细胞中，MHC-I蛋白的合成和转运通常发生在内质网和顺式高尔基体中，而表面MHC-I分子被迅速内化，积聚在内体囊泡中并被降解。Nef对MHC-I内吞作用的刺激代表了一种先前未记载的病毒逃避免疫反应的机制。
Like other pathogenic viruses, HIV-1 down-modulates surface expression of major histocompatibility complex class I (MHC-I) molecules in infected cells, thus impairing lysis by cytotoxic T lymphocytes(1,2). We have observed that this phenomenon depends on the expression of Nef. nef is an early gene of primate lentiviruses(3), which is necessary for maintaining high virus loads and inducing AIDS (ref. 4). Nef is not necessary for viral replication in vitro and stimulates the endocytosis of CD4 (ref. 5-8). We show that the expression of MHC-I at the surface of lymphoid, monocytic and epithelial cells was reduced in the presence of Nef protein from various HIV-1 strains. Whereas MHC-I protein synthesis and transport through the endoplasmic reticulum and cis Golgi apparatus occurred normally in Nef(+) cells, surface MHC-I molecules were rapidly internalized, accumulated in endosomal vesicles and were degraded. The stimulation of MHC-I endocytosis by Nef represents a previously undocumented viral mechanism for evading the immune response.