Plugging the Leak in Dengue Shock.

Recent structural and functional advances provide fresh insight into the biology of the dengue virus non-structural protein, NS1 and suggest new avenues of research. The work of our lab and others have shown that the secreted, hexameric form of NS1 has a systemic toxic effect, inducing inflammatory cytokines and acting directly on endothelial cells to produce the hallmark of dengue disease, vascular leak. We also demonstrated that NS1 exerts its toxic activity through recognition by the innate immune receptor TLR4, mimicking the bacterial endotoxin LPS. This monograph covers the background underpinning these new findings and discusses new avenues for antiviral and vaccine intervention.