Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis.
Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis.
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DOI：
10.1038/ncomms15576
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发表时间：
2017-06-08
影响因子：
16.6
通讯作者：
Amarasinghe GK
中科院分区：
文献类型：
--
作者：
Xu W;Luthra P;Wu C;Batra J;Leung DW;Basler CF;Amarasinghe GK
埃博拉病毒（EBOV）是一种有包膜的负义RNA病毒，可引起散发性疫情，病死率高。埃博拉病毒蛋白30（eVP 30）在EBOV核蛋白（eNP）基因处的转录起始中起关键作用，在复制周期如病毒组装中起额外作用。然而，目前还不清楚eVP 30在病毒复制周期中如何发挥作用的机制基础。在这里，我们定义了一个关键的相互作用之间的eVP 30和来自eNP的肽，这是很重要的，以促进相互作用，导致识别的RNA模板。我们目前的晶体结构的eVP 30 C-末端与此eNP肽复合物。eVP 30-eNP界面的功能分析鉴定了对病毒RNA合成至关重要的残基。总而言之，这些结果支持eVP 30-eNP相互作用在转录起始中起关键作用的模型，并为开发抗病毒治疗提供了新的靶点。埃博拉病毒（EBOV）VP 30是一种多功能蛋白质，在转录中发挥作用，但分子细节仍然未知。在这里，使用X射线晶体学和微型基因组测定，Xu等人定义了VP 30与NP的一部分之间的相互作用，这对于最佳EBOV RNA合成至关重要。
Ebola virus (EBOV) is an enveloped negative-sense RNA virus that causes sporadic outbreaks with high case fatality rates. Ebola viral protein 30 (eVP30) plays a critical role in EBOV transcription initiation at the nucleoprotein (eNP) gene, with additional roles in the replication cycle such as viral assembly. However, the mechanistic basis for how eVP30 functions during the virus replication cycle is currently unclear. Here we define a key interaction between eVP30 and a peptide derived from eNP that is important to facilitate interactions leading to the recognition of the RNA template. We present crystal structures of the eVP30 C-terminus in complex with this eNP peptide. Functional analyses of the eVP30–eNP interface identify residues that are critical for viral RNA synthesis. Altogether, these results support a model where the eVP30–eNP interaction plays a critical role in transcription initiation and provides a novel target for the development of antiviral therapy. Ebola virus (EBOV) VP30 is a multifunctional protein that plays a role in transcription, but molecular details remain unknown. Here, using X-ray crystallography and minigenome assays, Xu et al. define the interaction between VP30 and a portion of NP that is critical for optimal EBOV RNA synthesis.