Zika virus (ZIKV) has become a rising threat to human health due to its ability to cross placental barrier and cause fetal abnormalities, however the mechanism of its pathogenesis is still not fully understood. Previously, ZIKV infection in the human neural progenitor cells were reported to result in increased cell death and dysregulated cell-cycle progression by Ming <i>et al</i>. In our recent study, we established glycosaminoglycans (GAGs) as surface receptors in the human placenta that ZIKV host cell entry, however the role of GAGs in the human fetal brain was not investigated. In this study, human fetal neural progenitor cells derived from midbrain (VM) and forebrain (CX) and fully differentiated cells were used to model the human fetal brain. GAGs were isolated from these cells and subjected to 17 GAG disaccharide composition analysis using liquid chromatography mass spectrometry. In both undifferentiated and differentiated VM and CX cells, heparan sulfate (HS) was the main component of GAG (80.49-94.10%) while chondroitin sulfate (CS) and hyaluronan (HA) were minor components. In VM cells, percent disaccharide composition of HS NS6S, HS NS, HS 6S, and HA decreased while that of HS triS, HS 0S, and CS 4S increased upon differentiation. In CX cells, on the other hand, percent disaccharide composition of HS 0S, CS 4S, and HA decreased while only that of HS triS increased upon differentiation. Through “fishing” experiments, specific disaccharide structures of GAGs with high avidity for ZIKV envelope protein were also identified. This study uncovers GAG disaccharide composition of human fetal neural cells and their interactions with ZIKV envelope proteins to help us better understand the role of GAG in host cell invasion of ZIKV in fetal brain.

Glycosaminoglycan composition analysis of human fetal neural cells and their binding interactions with Zika virus envelope protein

254th National Meeting (2017)

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