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标题：The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection
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作者：Gergely Imre ; Verena Krähling ; Madeleine Eichler 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：4
页码：1-22
DOI：10.1016/j.isci.2021.102266
语种：English
出版社：Elsevier
摘要：SummaryEbola virus (EBOV) is responsible for outbreaks with case fatality rates of up to 90% and for an epidemic in West Africa with more than ten thousand deaths. EBOV glycoprotein (EBOV-GP) is the only viral surface protein and is responsible for viral entry into cells. Here, by employing pseudotyped EBOV-GP viral particles, we uncover a critical role for sphingolipids in inhibiting viral entry. Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P). The administration of the SphK1 activator, K6PC-5, or S1P, or the overexpression of SphK1 consistently exhibited striking inhibitory effects in EBOV-GP-driven entry in diverse cell lines. Finally, K6PC-5 markedly reduced the EBOV titer in infected cells and the de novo production of viral proteins. These data present K6PC-5 as an efficient tool to inhibit EBOV infection in endothelial cells and suggest further studies to evaluate its systemic effects.Graphical abstractDisplay OmittedHighlights•K6PC-5, a sphingosine kinase 1 activator, inhibits Ebola virus infection•Sphingosine 1-phosphate, the product of SphK1, attenuates the viral entry•Inhibiton/activation of S1P receptors has no influence on Ebola virus entry•These data support the endogen effect of S1P in Ebola virus infectionVirology ; Molecular Microbiology ; Cell Biology