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Science China Life Sciences

, Volume 57, Issue 10, pp 959–972 | Cite as

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

  • MiaoMiao Sheng
  • Ying Zhong
  • Yang Chen
  • JianChao Du
  • XiangWu Ju
  • Chen Zhao
  • GuiGen Zhang
  • LiFang Zhang
  • KangTai Liu
  • Ning Yang
  • Peng Xie
  • DangSheng Li
  • Michael Q. Zhang
  • ChengYu Jiang
Open Access
Research Paper Special Topic: Potential remedies against Ebola virus diseases

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.

Keywords

Ebola virus glycoprotein microRNAs cytotoxicity 

Supplementary material

11427_2014_4742_MOESM1_ESM.pdf (2 mb)
Supplementary material, approximately 2 MB.

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Copyright information

© The Author(s) 2014

Authors and Affiliations

  • MiaoMiao Sheng
    • 1
  • Ying Zhong
    • 1
  • Yang Chen
    • 2
  • JianChao Du
    • 1
  • XiangWu Ju
    • 1
  • Chen Zhao
    • 1
  • GuiGen Zhang
    • 1
  • LiFang Zhang
    • 1
  • KangTai Liu
    • 1
  • Ning Yang
    • 1
  • Peng Xie
    • 2
  • DangSheng Li
    • 3
  • Michael Q. Zhang
    • 2
    • 4
  • ChengYu Jiang
    • 1
    • 5
  1. 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 CollegeTsinghua UniversityBeijingChina
  2. 2.MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, TNLIST/Department of AutomationTsinghua UniversityBeijingChina
  3. 3.Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  4. 4.Department of Molecular and Cell Biology, Center for Systems BiologyThe University of TexasRL11 RichardsonUSA
  5. 5.State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China HospitalSichuan UniversityChengduChina

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