Zika Virus (ZIKV)'s ability to cause severe fetal anomalies led academic, federal, and industry research groups put urgent efforts to tackle ZIKV from basic, detection, and therapeutics research perspectives. While we are filling in the pieces of the whole picture of ZIKV, pathogenesis of related pathogenic flaviviruses has been well understood. Various pathogenic flaviviruses attach to glycosaminoglycans (GAGs) through their envelop protein and concentrate themselves on the surface of host cells as a first step in the process of pathogenesis. In this study, we utilized surface plasmon resonance (SPR) to screen various GAGs for their binding to envelope protein of ZIKV (ZIKV E). ZIKV E binds most strongly to heparin (HP), a most highly sulfated GAG, suggesting that the ZIKV E-GAG interaction is mainly electrostatically interaction driven as seen in other pathogenic flaviviruses. However, the order in which ZIKV E binds to various GAGs is not completely dependent upon the degree of sulfation showing that ZIKV E has specific saccharide sequence it prefers binding to. We also found that ZIKV E preferentially binds to longer chain HP oligosaccharides (12-18 saccharides) using SPR competition assays. Next, we isolated GAGs from human placentas and tested their binding to ZIKV E potentially mediating ZIKV to invade placenta prior to fetal infection. Both placental chondrotin sulfate and heparain sulfate GAGs showed micromolar interactions with ZIKV E. Finally we determined ZIKV E binding to porcine brain CS and HS, which showed relatively micromolar binding with ZIKV E. These results advance our understanding of ZIKV's pathogenesis and facilitate to develope therapeutics to effectively combat ZIKV with more insight.

Host cell entry of Zika virus may be mediated by glycosaminoglycans

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.