An important amino acid in nucleoprotein contributes to influenza A virus replication by interacting with polymerase PB2.
An important amino acid in nucleoprotein contributes to influenza A virus replication by interacting with polymerase PB2.
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DOI：
10.1016/j.virol.2014.06.033
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发表时间：
2014-09
期刊：
影响因子：
3.7
通讯作者：
X. Gui;Rui Li;Xuhui Zhang;Chenguang Shen;Hai Yu;Xiao-na Guo;Yahong Kang;Junyu Chen;
中科院分区：
文献类型：
--
作者：
X. Gui;Rui Li;Xuhui Zhang;Chenguang Shen;Hai Yu;Xiao-na Guo;Yahong Kang;Junyu Chen;
甲型流感病毒核蛋白（NP）在病毒核糖核蛋白（vRNP）复合物的形成中起着关键作用。然而，NP中的哪些关键残基与vRNP的组装相关并有助于病毒复制仍不清楚。在此，通过NP与广谱抗NP mAb 19 C10的Fv区的分子对接，鉴定了NP的残基88（D88）处的高度保守的天冬氨酸，并进一步证明其是有助于RNP活性的重要残基，病毒在MDCK细胞中的生长和在感染小鼠肺中的复制，通过比较重组野生型A/WSN/1933病毒转化为在NP残基88处含有丙氨酸而不是天冬氨酸的突变病毒。通过分子对接预测D88与PB 2相互作用，并通过免疫沉淀进一步验证。这些发现为理解病毒复制过程中NP与其他聚合酶亚基之间的相互作用提供了新的信息。
The nucleoprotein (NP) of influenza A virus plays a critical role in the formation of viral ribonucleoprotein (vRNP) complex. However, it remains unclear which key residues in NP are associated with the assembly of vRNP and contribute to virus replication. Here, a highly conserved aspartic acid at residue 88 (D88) of NP was identified by molecular docking of NP with the Fv region of a broad-spectrum anti-NP mAb 19C10 and further demonstrated to be an important residue contributes to the RNP activity, virus growth in MDCK cells and replication in lungs of infected mice by comparing recombinant wild-type A/WSN/1933 virus to the mutant virus that contains an alanine instead of aspartic acid at NP residue 88. D88 was also predicted to interact with PB2 by molecular docking and further verified by immunoprecipitation. These findings provide new information for understanding the interaction between NP and other polymerase subunits in virus replication.