Host factor SMYD3 is recruited by Ebola virus nucleoprotein to facilitate viral mRNA transcription
Host factor SMYD3 is recruited by Ebola virus nucleoprotein to facilitate viral mRNA transcription
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埃博拉病毒核蛋白招募宿主因子 SMYD3 促进病毒 mRNA 转录
DOI：
10.1080/22221751.2019.1662736
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发表时间：
2019-01-01
影响因子：
13.2
通讯作者：
Zhang, Junsong
中科院分区：
文献类型：
--
作者：
Chen, Jingliang;He, Zhangping;Zhang, Junsong
埃博拉病毒聚合酶复合体（EBOV）是病毒基因组转录和复制的功能单位。核蛋白（NP）是一种多功能蛋白，具有高RNA结合亲和力，并招募其他病毒蛋白形成功能性聚合酶复合物。在本研究中，我们通过质谱分析，研究了与EBOV聚合酶复合物相关的宿主蛋白，使用NP作为诱饵，在具有转录和复制能力的微型基因组系统中，鉴定了SET和MYND结构域包含蛋白3（SMYD 3）作为EBOV复制所需的新宿主蛋白。SMYD 3与NP特异性相互作用，并通过NP被募集到EBOV包涵体中。SMYD 3的耗尽显著抑制EBOV mRNA产生。非磷酸化VP 30的模拟物是一种转录激活因子，可以部分挽救因SMYD 3缺失而下调的病毒mRNA产生。此外，SMYD 3以剂量依赖性方式促进NP-VP 30相互作用。这些结果表明，SMYD 3是NP通过增加VP 30与NP的结合来支持EBOV mRNA转录的新宿主因子。因此，我们的研究为理解EBOV基因组转录机制提供了新的思路，并为以SMYD 3为靶点的抗EBOV药物设计提供了新的思路。
ABSTRACT The polymerase complex of Ebola virus (EBOV) is the functional unit for transcription and replication of viral genome. Nucleoprotein (NP) is a multifunctional protein with high RNA binding affinity and recruits other viral proteins to form functional polymerase complex. In our study, we investigated host proteins associated with EBOV polymerase complex using NP as bait in a transcription and replication competent minigenome system by mass spectrometry analysis and identified SET and MYND domain-containing protein 3 (SMYD3) as a novel host protein which was required for the replication of EBOV. SMYD3 specifically interacted with NP and was recruited to EBOV inclusion bodies through NP. The depletion of SMYD3 dramatically suppressed EBOV mRNA production. A mimic of non-phosphorylated VP30, which is a transcription activator, could partially rescue the viral mRNA production downregulated by the depletion of SMYD3. In addition, SMYD3 promoted NP-VP30 interaction in a dose-dependent manner. These results revealed that SMYD3 was a novel host factor recruited by NP to supporting EBOV mRNA transcription through increasing the binding of VP30 to NP. Thus, our study provided a new understanding of mechanism underlying the transcription of EBOV genome, and a novel anti-EBOV drug design strategy by targeting SMYD3.