25-hydroxycholesterol reduces inflammation, viral load and cell death in ZIKV-infected U-87 MG glial cell line

Abstract

Zika virus (ZIKV) infection is a global health issue due to its worldwide diffusion and to the related effects on neural progenitor cells with severe consequences on developing brain as well as on the central nervous system of adults. Previous studies showed that ZIKV infection induces an increment of IL1B expression in the central nervous system and also in the blood. IL-1β is a pro-inflammatory cytokine essential for cellular defence, tissue repair and neuroinflammation, a mechanism seen to be associated with several neuroinflammatory diseases. 25-hydroxycholesterol (25-HC) is a natural oxysterol, derived from hydroxylation of cholesterol, possessing important antiviral activity possibly correlated to its ability to alter host membrane structures. Furthermore, 25-HC is involved in the modulation of IL1B gene expression, being able to suppress IL-1β driven inflammation probably by blocking the activation of the SREB proteins. In our study, we analysed the antiviral action of 25-HC in ZIKV-infected U-87 MG cells, also evaluating its impact on inflammation and cell death. We demonstrated that 25-HC is able to reduce inflammation and cell death caused by ZIKV infection and also to diminish intracellular ZIKV load in U-87 MG glial cell line. Considering its antiviral activity and its ability to penetrate blood–brain barrier, 25-HC could be proposed, based on our results and literature findings, as a potential anti-ZIKV agent.

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Acknowledgements

The study has been supported by the Grant: MCTIC-CNPq/MEC-CAPES/MS-Decit/FNDCT No 14/2016—Prevenção e Combate ao vírus Zika and by the Grant 11/12 of the Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, Trieste, Italy. Robert Koch Institute (Berlin, Germany), supported by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 653316, generously provided the quantified Zika MR766 molecular standard. Prof. Del Sal G. (University of Trieste, Italy) generously provided U87-MG cells (human glioblastoma cell line).

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Correspondence to Paola Maura Tricarico.

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Tricarico, P.M., Caracciolo, I., Gratton, R. et al. 25-hydroxycholesterol reduces inflammation, viral load and cell death in ZIKV-infected U-87 MG glial cell line. Inflammopharmacol 27, 621–625 (2019). https://doi.org/10.1007/s10787-018-0517-6

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Keywords

  • ZIKV
  • Inflammation
  • 25-hydroxycholesterol
  • U-87 MG glial cell line