Description:

Microbiology-Immunology Seminar Series

"Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide. Systemic plasma leakage, leading to hypovolemic shock and potentially fatal complications, is a critical determinant of dengue severity. Recently, we described a novel pathogenic effect of dengue virus (DENV) non-structural protein 1 (NS1) in triggering permeability of human endothelial cells in vitro and systemic vascular leakage in vivo. We also showed that vaccination with recombinant DENV NS1 or passive transfer of NS1-immune serum or anti-NS1 monoclonal antibodies protects against lethal DENV-induced vascular leak. We have now demonstrated a new mechanism by which NS1 directly triggers vascular dysfunction through the early enzymatic activation and cleavage of the endothelial glycocalyx and extracellular matrix as well as disassembly of intercellular junctions, resulting in endothelial hyperpermeability. Overall, these findings add an important and previously-overlooked component to the causes of dengue-induced vascular leak, identify a new potential target for anti-dengue therapeutics, and support inclusion of NS1 in dengue vaccines."

Eva Harris, PhD

University of California, Berkeley

Host: Virology Students & Postdocs