Zika virus propagation and release in human fetal astrocytes can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869

Yunlong Huang, Yuju Li, Hainan Zhang, Runze Zhao, Ran Jing, Yinghua Xu, Miao He, Justin Peer, Yeong C. Kim, Jiangtao Luo, Zenghan Tong, Jialin C Zheng

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Zika virus (ZIKV) is a neurotrophic flavivirus that is capable of infecting humans, leading to brain abnormalities during fetal development. The ZIKV infectivity in neural target cells remains poorly understood. Here, we found that ZIKV specifically infected glial fibrillary acidic protein- and S100B-positive primary human astrocytes derived from fetal brains. In contrast, neuron-specific Class III β-tubulin (TuJ1)-positive neurons in the astrocyte cultures and SOX2-positive neural progenitor cells derived from the fetal brains were less susceptible to ZIKV infection compared with astrocytes. The infected astrocytes released competent viral particles and manifested programmed cell death with a progressive cytopathic effect. Interestingly, ZIKV infection in human fetal astrocytes induced a significant increase of extracellular vesicles (EVs). Treatment with GW4869, a specific inhibitor of neutral sphingomyelinase-2, decreased EV levels, suppressed ZIKV propagation, and reduced the release of infectious virions in astrocytes. Therefore, ZIKV infects primary human fetal astrocytes and the infection can be suppressed by neutral sphingomyelinase-2 inhibitor GW4869. Further investigation into sphingomyelin metabolism and EVs may provide insights to the therapeutic treatment of ZIKV infection.

Original languageEnglish (US)
Article number19
JournalCell Discovery
Volume4
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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