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Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection.

Publication ,  Journal Article
Kim, SY; Koetzner, CA; Payne, AF; Nierode, GJ; Yu, Y; Wang, R; Barr, E; Dordick, JS; Kramer, LD; Zhang, F; Linhardt, RJ
Published in: Biochemistry
February 26, 2019

Zika virus (ZIKV) is an enveloped RNA virus from the flavivirus family that can cause fetal neural abnormalities in pregnant women. Previously, we established that ZIKV-EP (envelope protein) binds to human placental chondroitin sulfate (CS), suggesting that CS may be a potential host cell surface receptor in ZIKV pathogenesis. In this study, we further characterized the GAG disaccharide composition of other biological tissues (i.e., mosquitoes, fetal brain cells, and eye tissues) in ZIKV pathogenesis to investigate the role of tissue specific GAGs. Heparan sulfate (HS) was the major GAG, and levels of HS-6-sulfo, HS 0S (unsulfated HS), and CS 4S disaccharides were the main differences in the GAG composition of Aedes aegypti and Aedes albopictus mosquitoes. In human fetal neural progenitor and differentiated cells, HS 0S and CS 4S were the main disaccharides. A change in disaccharide composition levels was observed between undifferentiated and differentiated cells. In different regions of the bovine eyes, CS was the major GAG, and the amounts of hyaluronic acid or keratan sulfate varied depending on the region of the eye. Next, we examined heparin (HP) of various structures to investigate their potential in vitro antiviral activity against ZIKV and Dengue virus (DENV) infection in Vero cells. All compounds effectively inhibited DENV replication; however, they surprisingly promoted ZIKV replication. HP of longer chain lengths more strongly promoted activity in ZIKV replication. This study further expands our understanding of role of GAGs in ZIKV pathogenesis and carbohydrate-based antivirals against flaviviral infection.

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Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

February 26, 2019

Volume

58

Issue

8

Start / End Page

1155 / 1166

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Virus Replication
  • Virus Internalization
  • Vero Cells
  • Neural Stem Cells
  • Mosquito Vectors
  • In Vitro Techniques
  • Humans
  • Heparitin Sulfate
 

Citation

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Kim, S. Y., Koetzner, C. A., Payne, A. F., Nierode, G. J., Yu, Y., Wang, R., … Linhardt, R. J. (2019). Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection. Biochemistry, 58(8), 1155–1166. https://doi.org/10.1021/acs.biochem.8b01267
Kim, So Young, Cheri A. Koetzner, Anne F. Payne, Gregory J. Nierode, Yanlei Yu, Rufeng Wang, Evan Barr, et al. “Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection.Biochemistry 58, no. 8 (February 26, 2019): 1155–66. https://doi.org/10.1021/acs.biochem.8b01267.
Kim, So Young, et al. “Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection.Biochemistry, vol. 58, no. 8, Feb. 2019, pp. 1155–66. Pubmed, doi:10.1021/acs.biochem.8b01267.
Kim SY, Koetzner CA, Payne AF, Nierode GJ, Yu Y, Wang R, Barr E, Dordick JS, Kramer LD, Zhang F, Linhardt RJ. Glycosaminoglycan Compositional Analysis of Relevant Tissues in Zika Virus Pathogenesis and in Vitro Evaluation of Heparin as an Antiviral against Zika Virus Infection. Biochemistry. 2019 Feb 26;58(8):1155–1166.
Journal cover image

Published In

Biochemistry

DOI

EISSN

1520-4995

Publication Date

February 26, 2019

Volume

58

Issue

8

Start / End Page

1155 / 1166

Location

United States

Related Subject Headings

  • Zika Virus Infection
  • Zika Virus
  • Virus Replication
  • Virus Internalization
  • Vero Cells
  • Neural Stem Cells
  • Mosquito Vectors
  • In Vitro Techniques
  • Humans
  • Heparitin Sulfate