Using Bioorthogonal Chemistry for Investigating Dengue Virus Interactome
PublisherThe University of Arizona.
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AbstractA mosquito-borne virus endemic to the tropics and subtropics, dengue (DENV) is the most common arbovirus in the world. Among other obstacles, an incomplete understanding of specific host-virus protein-protein interactions (PPI) challenges the development of vaccines and antiviral therapies for DENV. Previous studies on DENV PPI depend on genetic modifications, which can be tedious and time-consuming to accomplish. Mixing the principles of chemical biology and virology, the work in this thesis aims to take advantage of chemical modifications on DENV to pull down DENV-host PPI. First, this thesis will present the chemical modification of the DENV E glycoprotein via the metabolic incorporation of an unnatural sugar. This modification seemed to produce a morphology change in the viral structure, rendering it an impractical chemical modification. Then, this thesis will introduce an attempt to use bioorthogonal chemical modifications to DENV to pull down an established DENV PPI with an antibody as a proof-of-concept experiment to demonstrate the possibility of using bioorthogonal chemistry for identifying DENV PPI. Currently, this experiment is stalled by the presentation of background labelling. In the future, we hope to optimize the pull-down proof-of-concept and later use the same protocol to identifying PPI in DENV-infected mosquitoes.
Degree ProgramHonors College