Glycosaminoglycans in infectious diseases

Authors
Kim, So Young
ORCID
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Other Contributors
Linhardt, Robert J.
Barquera, Blanca L.
Koffas, Mattheos A. G.
Wang, Chunyu
Issue Date
2018-12
Keywords
Biochemistry and biophysics
Degree
PhD
Terms of Use
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
Full Citation
Abstract
Glycosaminoglycans (GAGs) are anionic linear polysaccharides with a repeating disaccharide unit. Located on cell surface and extracellular matrix, GAGs are involved in key biological processes including cellular signaling, immunity, and pathogenesis. Various bacterial, viral, and parasitic pathogens successfully invade host cells through interacting with host cell surface GAGs, which result in many pathological processes, such as adhesion, cell-to-cell communication, biochemical cascades, and the immune response. For example, pathogenic flaviviruses like dengue and West Nile virus (DENV & WNV) bind host cell surface GAGs through their surface envelope proteins as a first step in the host cell invasion. In the past few years, another flavivirus Zika virus (ZIKV) has become a global human health threat due to its unique ability to cross placental barrier and cause fetal anomalies in pregnant women, however the role of GAGs had not been investigated prior to my dissertation work. Based on great structural similarities between ZIKV and DENV envelope proteins, we hypothesized that ZIKV envelope protein may also bind GAGs during host cell invasion of placenta. The GAG composition analysis based on liquid chromatography mass spectrometry method revealed that chondroitin sulfate (CS) is the major GAG in human placenta and we discovered subnanomolar binding interactions between human placental CS and ZIKV envelope protein suggesting that ZIKV may utilize host cell surface GAGs during vertical transmission of human placenta. Building on these findings, we further characterized GAG disaccharide composition of additional relevant tissues (Aedes mosquitoes, human fetal neural progenitor cells, and eye tissues) and discussed their potential involvement in ZIKV pathogenesis.
Description
December 2018
School of Science
Department
Biochemistry and Biophysics Program
Publisher
Rensselaer Polytechnic Institute, Troy, NY
Relationships
Rensselaer Theses and Dissertations Online Collection
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