title: Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of Ebola virus glycoprotein in vitro.
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.
authors.affiliation: 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.
authors.forename: MiaoMiao
authors.initials: M
authors.lastname: Sheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhong
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: JianChao
authors.initials: J
authors.lastname: Du
authors.forename: XiangWu
authors.initials: X
authors.lastname: Ju
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: GuiGen
authors.initials: G
authors.lastname: Zhang
authors.forename: LiFang
authors.initials: L
authors.lastname: Zhang
authors.forename: KangTai
authors.initials: K
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.forename: DangSheng
authors.initials: D
authors.lastname: Li
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.forename: ChengYu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival; D049030:Dystroglycans / Q000378:metabolism; D029043:Ebolavirus; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D008074:Lipoproteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D008074:Lipoproteins; C577700:MIRN1246 microRNA, human; C542543:MIRN196 microRNA, human; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; C051928:lipoprotein-associated coagulation inhibitor; D049030:Dystroglycans; C505530:CASP8 protein, human; D053181:Caspase 8