[转移贴]PNAS：揭开免疫系统消灭病毒机制 有助抗病毒药物研发

viruskiller

原贴由stare024 发表于 2010-11-18 11:27

生物谷11.4日报道：
    长期以来医学界认为，人体免疫系统对已进入细胞内部的病毒束手无策。但英国一项最新研究发现，一些抗体能够随病毒进入人体细胞内部，并在细胞内一种蛋白质的作用下引发摧毁病毒的连锁反应，这一发现将有助于研发新的抗病毒药物。

    位于英国剑桥的分子生物学实验室等机构研究人员在新一期美国《国家科学院学报》上报告说，他们发现人体免疫系统生成的抗体在血液中遇到病毒后，会一直附着其上，即使一些病毒穿过细胞膜进入了人体细胞，抗体也仍然附着于这些病毒表面。而人体细胞内部一种名为TRIM21的蛋白质会发现这些抗体，并激活细胞内部的“垃圾处理系统”，在较短时间内将病毒消灭。

    研究人员已经开始尝试在此基础上研发新的抗病毒药物。初步实验显示，在增加细胞中TRIM21蛋白质的含量后，细胞消灭病毒的能力大大提高。

原文链接：PNAS的全文是免费的，就看你网速够不够快了。
http://www.pnas.org/content/early/2010/11/01/1014074107.abstract

Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)

Antibodies provide effective antiviral immunity despite the fact that viruses escape into cells when they infect. Here we show that antibodies remain attached to viruses after cell infection and mediate an intracellular immune response that disables virions in the cytosol. We have discovered that cells possess a cytosolic IgG receptor, tripartite motif-containing 21 (TRIM21), which binds to antibodies with a higher affinity than any other IgG receptor in the human body. TRIM21 rapidly recruits to incoming antibody-bound virus and targets it to the proteasome via its E3 ubiquitin ligase activity. Proteasomal targeting leads to rapid degradation of virions in the cytosol before translation of virally encoded genes. Infection experiments demonstrate that at physiological antibody concentrations TRIM21 neutralizes viral infection. These results reveal an intracellular arm of adaptive immunity in which the protection mediated by antibodies does not end at the cell membrane but continues inside the cell to provide a last line of defense against infection.