PDF(Pubmed)
Abstract：
Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses. Here, we find that IFN alters the subcellular localization of hundreds of host proteins, and this IFN effect is partially lost upon MXB depletion. The results of our mechanistic study reveal that MXB recognizes vimentin (VIM) and recruits protein kinase B (AKT) to phosphorylate VIM at amino acid S38, which leads to reorganization of the VIM network and impairment of intracellular trafficking of virus protein complexes, hence causing a restriction of virus infection. These results highlight a new function of MXB in modulating VIM-mediated trafficking, which may lead towards a novel broad-spectrum antiviral strategy to control a large group of viruses that depend on VIM for successful replication.
摘要：
I型干扰素(IFN)通过刺激抗病毒蛋白的表达抑制广谱的病毒。作为IFN诱导的蛋白质，据报道，粘液病毒抗性B（MXB）蛋白可以抑制多种高致病性人类病毒。MXB是否采用通用机制来限制不同的病毒仍有待确定。这里,我们发现IFN改变了数百种宿主蛋白的亚细胞定位，并且这种IFN效应在MXB耗尽时部分丧失。我们的机制研究结果表明，MXB识别波形蛋白（VIM）并募集蛋白激酶B（AKT）在氨基酸S38处磷酸化VIM，这导致VIM网络的重组和病毒蛋白质复合物的细胞内运输的损害，从而导致病毒感染的限制。这些结果突出了MXB在调节VIM介导的贩运中的新功能，这可能导致一种新型的广谱抗病毒策略来控制一大群依赖于VIM成功复制的病毒。
