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

• DOI: 10.1038/s41421-018-0017-2
• Publication Date: 2018-04-18T12:28:20Z
• Authors: Yunlong Huang; Yuju Li; Hainan Zhang; Runze Zhao; Ran Jing; Yinghua Xu; Miao He; Justin Peer; Yeong C. Kim; Jiangtao Luo; Zenghan Tong; Jialin Zheng
• Keywords: Infectivity; Zika Virus; Cytopathic effect

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