Edwina Tran L&S Sciences
Molecular determinants of DENV NS1-mediated endothelial barrier dysfunction
Dengue virus (DENV) is a mosquito-borne flavivirus that causes up to 390 million infections every year, resulting in 96 million cases of disease globally. Infection with any of the four serotypes of dengue can result in inapparent infection, dengue fever, or severe forms of the disease associated with vascular leak leading to shock. DENV non-structural protein 1 (NS1) plays a role in viral replication and immune evasion, as well as pathogenesis. More specifically, DENV NS1 has been found to trigger permeability of human endothelial cells in vitro and systemic vascular leak in vivo.
This summer, my research project investigates the hypothesis that the structure and glycosylation status of secreted NS1 (sNS1) affect its interaction with the endothelium and activation of signaling pathways leading to vascular barrier dysfunction, and that these functions are determined by specific amino acids of NS1. By modifying specific features of NS1 structure, I hope to define the determinants of NS1 effects on the microvasculature. Identification of the key target NS1 regions is crucial to understanding DENV pathogenesis and the human immune response against the pathogen, as well as for developing antiviral therapies and NS1-based vaccine approaches.