Kendall E. Lee L&S Sciences
Binding Determinants of Dengue Virus NS1 to Human Endothelial Cells
Dengue virus (DENV) is the most prevalent mosquito-borne virus worldwide, causing ~390 million infections annually. Disease ranges from inapparent infection to classic dengue fever to severe dengue, characterized by vascular leak that can lead to systemic shock, organ failure, and death.
Non-structural protein 1 (NS1) is the only protein secreted from DENV-infected cells and plays a role in pathogenesis through induction of barrier dysfunction of human endothelial cells. However, the receptor for NS1 on endothelial cells and the molecular determinants of pathogenesis on NS1 remain unknown.
In my research, I seek to identify specific DENV NS1 regions that are required for binding to human endothelial cells and to investigate whether blocking these binding sites prevents NS1-induced pathogenesis. My experimental approach includes testing a panel of anti-NS1 monoclonal antibodies to determine which antibodies prevent NS1 binding to human pulmonary microvascular endothelial cells (HPMEC). Then, the NS1 epitope targeted by these antibodies will be mapped to elucidate the residues involved in cell surface binding. This key information could form the foundation for developing NS1-based therapeutic treatments.