HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway.
HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway.
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DOI：
10.1006/viro.2000.0816
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发表时间：
2001-04
期刊：
影响因子：
3.7
通讯作者：
S. A. Swann;Maya Williams;C. Story;K. Bobbitt;Rebekah I. Fleis;K. Collins
中科院分区：
文献类型：
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作者：
S. A. Swann;Maya Williams;C. Story;K. Bobbitt;Rebekah I. Fleis;K. Collins
艾滋病毒通过逃避免疫根除而引起慢性感染。HIV免疫逃逸的一个关键因素是HIV-1 Nef蛋白。Nef导致细胞表面主要组织相容性复合物I类（MHC-I）蛋白表达水平的降低，从而保护HIV感染的细胞免受抗HIV细胞毒性T淋巴细胞（CTL）的识别和杀伤。Nef还通过加速内吞作用降低HIV受体CD 4的细胞表面水平。我们在这里表明，内吞作用是不需要Nef介导的下调MHC-I分子。Nef的主要作用是阻止MHC-I分子转运到细胞表面，导致在细胞内细胞器中积累。此外，Nef对MHC-I分子（但不对CD 4）的作用需要磷酸肌醇3-激酶（PI 3-激酶）活性。我们认为Nef将MHC-1蛋白转移到PI 3激酶依赖的转运途径中，从而阻止细胞表面的表达。
HIV causes a chronic infection by evading immune eradication. A key element of HIV immune escape is the HIV-1 Nef protein. Nef causes a reduction in the level of cell surface major histocompatibility complex class I (MHC-I) protein expression, thus protecting HIV-infected cells from anti-HIV cytotoxic T lymphocyte (CTL) recognition and killing. Nef also reduces cell surface levels of the HIV receptor, CD4, by accelerating endocytosis. We show here that endocytosis is not required for Nef-mediated downmodulation of MHC-I molecules. The main effect of Nef is to block transport of MHC-I molecules to the cell surface, leading to accumulation in intracellular organelles. Furthermore, the effect of Nef on MHC-I molecules (but not on CD4) requires phosphoinositide 3-kinase (PI 3-kinase) activity. We propose that Nef diverts MHC-1 proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface.