MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
J Virol. 2012 Aug;86(16):8482-91. doi: 10.1128/JVI.00728-12. Epub 2012 May 30.
Despite a central role in immunity, antibody neutralization of virus infection is poorly understood. Here we show how the neutralization and persistence of adenovirus type 5, a prevalent nonenveloped human virus, are dependent upon the intracellular antibody receptor TRIM21. Cells with insufficient amounts of TRIM21 are readily infected, even at saturating concentrations of neutralizing antibody. Conversely, high TRIM21 expression levels decrease the persistent fraction of the infecting virus and allows neutralization by as few as 1.6 antibody molecules per virus. The direct interaction between TRIM21 and neutralizing antibody is essential, as single-point mutations within the TRIM21-binding site in the Fc region of a potently neutralizing antibody impair neutralization. However, infection at high multiplicity can saturate TRIM21 and overcome neutralization. These results provide insight into the mechanism and importance of a newly discovered, effector-driven process of antibody neutralization of nonenveloped viruses.
尽管在免疫中起着核心作用，但人们对抗体中和病毒感染的机制仍知之甚少。在这里，我们展示了腺病毒 5 型（一种常见的非包膜人类病毒）的中和和持续存在是如何依赖于细胞内抗体受体 TRIM21 的。TRIM21 含量不足的细胞很容易被感染，即使在中和抗体的饱和浓度下也是如此。相反，高表达 TRIM21 水平会降低感染病毒的持续分数，并允许每病毒只需 1.6 个抗体分子即可中和。TRIM21 和中和抗体之间的直接相互作用是至关重要的，因为在一种强效中和抗体的 Fc 区域内的 TRIM21 结合位点中的单点突变会损害中和作用。然而，高倍数的感染可以使 TRIM21 饱和并克服中和作用。这些结果为我们深入了解新发现的、效应驱动的非包膜病毒抗体中和机制及其重要性提供了线索。
