Schwartz O, Maréchal V, Le Gall S, Lemonnier F, Heard J M
Laboratoire Rétrovirus et Transfert Génétique, Unité de Recherche Associée CNRS 1157, Paris, France.
Nat Med. 1996 Mar;2(3):338-42. doi: 10.1038/nm0396-338.
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. We have observed that this phenomenon depends on the expression of Nef. nef is an early gene of primate lentiviruses, which is necessary for maintaining high virus loads and inducing AIDS. Nef is not necessary for viral replication in vitro and stimulates the endocytosis of CD4. 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.
与其他致病性病毒一样，HIV-1会下调受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淋巴细胞的裂解作用。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，对于维持高病毒载量和诱导艾滋病是必需的。Nef在体外病毒复制中并非必需，且会刺激CD4的内吞作用。我们发现，在存在来自各种HIV-1毒株的Nef蛋白的情况下，淋巴、单核细胞和上皮细胞表面的MHC-I表达会降低。虽然MHC-I蛋白的合成以及通过内质网和顺式高尔基体的运输在Nef(+)细胞中正常发生，但表面MHC-I分子会迅速内化，积聚在内体小泡中并被降解。Nef对MHC-I内吞作用的刺激代表了一种以前未被记录的逃避免疫反应的病毒机制。
