HMGB1 Protein Binds to Influenza Virus Nucleoprotein and Promotes Viral Replication
HMGB1 Protein Binds to Influenza Virus Nucleoprotein and Promotes Viral Replication
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DOI：
10.1128/jvi.00789-12
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发表时间：
2012-09-01
影响因子：
5.4
通讯作者：
Jestin, Jean-Luc
中科院分区：
文献类型：
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作者：
Moisy, Dorothee;Avilov, Sergiy V.;Jestin, Jean-Luc
流感病毒已经进化出劫持宿主细胞途径的复制策略。为了揭示病毒大分子和宿主蛋白之间的相互作用，我们应用了噬菌体展示策略。将展示在丝状噬菌体上的人cDNA表达产物的文库提交用于流感病毒核糖核蛋白（vRNP）的亲和选择。发现高迁移率族蛋白（HMGB）蛋白与vRNP的核蛋白（NP）组分结合。HMGB1和HMGB2在不存在病毒RNA的情况下直接结合纯化的NP，并且HMG盒A结构域足以结合NP。我们发现，HMGB1与感染细胞核中的病毒NP相关联，促进病毒生长，并增强病毒聚合酶的活性。功能性HMGB1 DNA结合位点的存在是增强流感病毒复制所必需的。降低HMGBI与DNA结合的甘草甜素抑制流感病毒聚合酶活性。我们的数据表明，HMGBI蛋白可以在流感病毒的核内复制中发挥重要作用，从而扩展了先前对博尔纳病毒和一些DNA病毒的研究结果。
Influenza virus has evolved replication strategies that hijack host cell pathways. To uncover interactions between viral macromolecules and host proteins, we applied a phage display strategy. A library of human cDNA expression products displayed on filamentous phages was submitted to affinity selection for influenza viral ribonucleoproteins (vRNPs). High-mobility-group box (HMGB) proteins were found to bind to the nucleoprotein (NP) component of vRNPs. HMGB1 and HMGB2 bind directly to the purified NP in the absence of viral RNA, and the HMG box A domain is sufficient to bind the NP. We show that HMGB1 associates with the viral NP in the nuclei of infected cells, promotes viral growth, and enhances the activity of the viral polymerase. The presence of a functional HMGB1 DNA-binding site is required to enhance influenza virus replication. Glycyrrhizin, which reduces HMGBI binding to DNA, inhibits influenza virus polymerase activity. Our data show that the HMGBI protein can play a significant role in intranuclear replication of influenza viruses, thus extending previous findings on the bornavirus and on a number of DNA viruses.