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Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro

Science China Life Sciences volume 57, pages 959–972 (2014)Cite this article

Abstract

Ebola virus (EBOV) causes a highly lethal hemorrhagic fever syndrome in humans and has been associated with mortality rates of up to 91% in Zaire, the most lethal strain. Though the viral envelope glycoprotein (GP) mediates widespread inflammation and cellular damage, these changes have mainly focused on alterations at the protein level, the role of microRNAs (miRNAs) in the molecular pathogenesis underlying this lethal disease is not fully understood. Here, we report that the mi-RNAs hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p were induced in human umbilical vein endothelial cells (HUVECs) following expression of EBOV GP. Among the proteins encoded by predicted targets of these miRNAs, the adhesion-related molecules tissue factor pathway inhibitor (TFPI), dystroglycan1 (DAG1) and the caspase 8 and FADD-like apoptosis regulator (CFLAR) were significantly downregulated in EBOV GP-expressing HUVECs. Moreover, inhibition of hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p, or overexpression of TFPI, DAG1 and CFLAR rescued the cell viability that was induced by EBOV GP. Our results provide a novel molecular basis for EBOV pathogenesis and may contribute to the development of strategies to protect against future EBOV pandemics.

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Affiliations

  1. State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; Department of Biochemistry and Molecular Biology, Peking Union Medical College, Tsinghua University, Beijing, 100005, China

    MiaoMiao Sheng, Ying Zhong, JianChao Du, XiangWu Ju, Chen Zhao, GuiGen Zhang, LiFang Zhang, KangTai Liu, Ning Yang & ChengYu Jiang

  2. MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, 100084, China

    Yang Chen, Peng Xie & Michael Q. Zhang

  3. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    DangSheng Li

  4. Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas 800 West Campbell Road, RL11 Richardson, TX, 75080-3021, USA

    Michael Q. Zhang

  5. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610000, China

    ChengYu Jiang

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  1. MiaoMiao Sheng
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Correspondence to Michael Q. Zhang or ChengYu Jiang.

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Sheng, M., Zhong, Y., Chen, Y. et al. Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro. Sci. China Life Sci. 57, 959–972 (2014). https://doi.org/10.1007/s11427-014-4742-y

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Keywords

  • Ebola virus
  • glycoprotein
  • microRNAs
  • cytotoxicity