Glycosaminoglycans in infectious diseases

dc.contributorLinhardt, Robert J.
dc.contributorBarquera, Blanca L.
dc.contributorKoffas, Mattheos A. G.
dc.contributorWang, Chunyu
dc.contributor.authorKim, So Young
dc.descriptionDecember 2018
dc.descriptionSchool of Science
dc.description.abstractGlycosaminoglycans (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.
dc.publisherRensselaer Polytechnic Institute, Troy, NY
dc.relation.departmentBiochemistry and Biophysics Program
dc.relation.ispartofRensselaer Theses and Dissertations Online Collection
dc.rights.holderThis electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
dc.rights.licenseRestricted to current Rensselaer faculty, staff and students. Access inquiries may be directed to the Rensselaer Libraries.
dc.subjectBiochemistry and biophysics
dc.titleGlycosaminoglycans in infectious diseases
dc.typeElectronic thesis
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