Protein and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19985-90. doi: 10.1073/pnas.1014074107. Epub 2010 Nov 2.
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.
尽管病毒在感染时会逃入细胞，但抗体提供了有效的抗病毒免疫。在这里，我们表明抗体在细胞感染后仍附着在病毒上，并介导一种细胞内免疫反应，使胞质中的病毒失活。我们发现细胞具有胞质 IgG 受体，三结构域蛋白 21（TRIM21），它与抗体的结合亲和力高于人体中任何其他 IgG 受体。TRIM21 迅速募集到进入的抗体结合病毒，并通过其 E3 泛素连接酶活性将其靶向蛋白酶体。蛋白酶体靶向导致病毒在细胞质中的翻译之前迅速降解病毒。感染实验表明，在生理抗体浓度下，TRIM21 中和病毒感染。这些结果揭示了适应性免疫的细胞内分支，其中抗体介导的保护不仅在细胞膜结束，而且在细胞内继续，为抵抗感染提供了最后一道防线。
