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    Glycosaminoglycan compositional analysis of relevant tissues in ZIKV pathogenesis and in vitro evaluation of heparin as antiviral against ZIKV infection

    Author
    Kim, S.Y.; Koetzner, C.A.; Payne, A.F.; Nierode, G.J.; Yu, Y.; Wang, R.; Barr, E.; Dordick, J.S.; Kramer, L.D.; Zhang, F.; Linhardt, Robert J.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    GLYCOSAMINOGLYCAN COMPOSITIONAL ANALYSIS OF RELEVANT TISSUES.pdf (1.727Mb)
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    Date Issued
    2019
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Glycosaminoglycan compositional analysis of relevant tissues in ZIKV pathogenesis and in vitro evaluation of heparin as antiviral against ZIKV infection, S.Y. Kim, C.A. Koetzner, A.F. Payne, G.J. Nierode, Y. Yu, R. Wang, E. Barr, J.S. Dordick, L.D. Kramer, F. Zhang, R.J. Linhardt, Biochemistry, 58, 1155–1166, 2019.
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    URI
    https://hdl.handle.net/20.500.13015/5369; https://doi.org/10.1021/acs.biochem.8b01267
    Abstract
    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.;
    Description
    Biochemistry, 58, 1155–1166; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    American Chemical Society (ACS)
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; https://harc.rpi.edu/;
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