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Host factor SMYD3 is recruited by Ebola virus nucleoprotein to facilitate viral mRNA transcription

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posted on 2019-09-13, 11:25 authored by Jingliang Chen, Zhangping He, Yaochang Yuan, Feng Huang, Baohong Luo, Jianhua Zhang, Ting Pan, Hui Zhang, Junsong Zhang

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.

Funding

The present study was supported by the National Special Research Program of China for Important Infectious Diseases (2018ZX10302103, 2017ZX10202102-003, and 2018ZX10101004003001), the Important Key Program of Natural Science Foundation of China (81730060), the International Collaboration Program of Natural Science Foundation of China and US NIH (81561128007), the Joint-innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou (201803040002), and the National Natural Science Foundation of China (81601759, and 81701990).

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