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Interaction of Zika Virus Envelope Protein with Glycosaminoglycans.

Publication ,  Journal Article
Kim, SY; Zhao, J; Liu, X; Fraser, K; Lin, L; Zhang, X; Zhang, F; Dordick, JS; Linhardt, RJ
Published in: Biochemistry
February 28, 2017

In February 2016, the World Health Organization declared a Public Health Emergency of International Concern on Zika Virus (ZIKV), because of its association with severe fetal anomalies of congenitally infected humans. This has led to urgent efforts by academic, federal, and industry research groups to improve our understanding of the pathogenesis of ZIKV and to develop detection methods, therapeutic strategies, and vaccines. Although we still do not have the entire picture of the pathogenesis of ZIKV, extensive research has been conducted on related pathogenic flaviviruses (i.e., dengue virus, West Nile virus, and yellow fever virus). Binding to glycosaminoglycans (GAGs) through its envelope protein is the first step in successful host cell invasion of dengue virus. In this study, we examined ZIKV envelope protein (ZIKV E) binding to GAGs in a real time interaction study using surface plasmon resonance (SPR) to explore the role of GAGs in host cell entry of ZIKV into placenta and brain. ZIKV E strongly binds (KD = 443 nM) pharmaceutical heparin (HP), a highly sulfated GAG, and binds with lower avidity to less sulfated GAGs, suggesting that the ZIKV E-GAG interaction may be electrostatically driven. Using SPR competition assays with various chain length HP oligosaccharides (from 4 to 18 saccharide units in length), we observed that ZIKV E preferentially binds to longer HP oligosaccharides (with 8-18 saccharides). Next, we examined GAGs prepared from human placentas to determine if they bound ZIKV E, possibly mediating placental cell invasion of ZIKV. Compositional analysis of these GAGs as well as SPR binding studies showed that both chondroitin sulfate and heparan sulfate GAGs, present on the placenta, showed low-micromolar interactions with ZIKV E. Both porcine brain CS and HS also showed micromolar binding with ZIKV E. Moreover, heparan sulfate with a higher TriS content, the dominant repeating unit of HP, shows a high affinity for ZIKV E. These results suggest that GAGs may be utilized as attachment factors for host cell entry of Zika virus as they do in other pathogenic flaviviruses. They may also assist us in advancing our understanding of the pathogenesis of ZIKV and guide us in designing therapeutics to combat ZIKV with more insight.

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Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

February 28, 2017

Volume

56

Issue

8

Start / End Page

1151 / 1162

Location

United States

Related Subject Headings

  • Zika Virus
  • Viral Envelope Proteins
  • Swine
  • Surface Plasmon Resonance
  • Substrate Specificity
  • Protein Conformation
  • Protein Binding
  • Pregnancy
  • Placenta
  • Models, Molecular
 

Citation

APA
Chicago
ICMJE
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Kim, S. Y., Zhao, J., Liu, X., Fraser, K., Lin, L., Zhang, X., … Linhardt, R. J. (2017). Interaction of Zika Virus Envelope Protein with Glycosaminoglycans. Biochemistry, 56(8), 1151–1162. https://doi.org/10.1021/acs.biochem.6b01056
Kim, So Young, Jing Zhao, Xinyue Liu, Keith Fraser, Lei Lin, Xing Zhang, Fuming Zhang, Jonathan S. Dordick, and Robert J. Linhardt. “Interaction of Zika Virus Envelope Protein with Glycosaminoglycans.Biochemistry 56, no. 8 (February 28, 2017): 1151–62. https://doi.org/10.1021/acs.biochem.6b01056.
Kim SY, Zhao J, Liu X, Fraser K, Lin L, Zhang X, et al. Interaction of Zika Virus Envelope Protein with Glycosaminoglycans. Biochemistry. 2017 Feb 28;56(8):1151–62.
Kim, So Young, et al. “Interaction of Zika Virus Envelope Protein with Glycosaminoglycans.Biochemistry, vol. 56, no. 8, Feb. 2017, pp. 1151–62. Pubmed, doi:10.1021/acs.biochem.6b01056.
Kim SY, Zhao J, Liu X, Fraser K, Lin L, Zhang X, Zhang F, Dordick JS, Linhardt RJ. Interaction of Zika Virus Envelope Protein with Glycosaminoglycans. Biochemistry. 2017 Feb 28;56(8):1151–1162.
Journal cover image

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

February 28, 2017

Volume

56

Issue

8

Start / End Page

1151 / 1162

Location

United States

Related Subject Headings

  • Zika Virus
  • Viral Envelope Proteins
  • Swine
  • Surface Plasmon Resonance
  • Substrate Specificity
  • Protein Conformation
  • Protein Binding
  • Pregnancy
  • Placenta
  • Models, Molecular