Skip to Main content Skip to Navigation
Journal articles

Dengue virus NS1 protein conveys pro‐inflammatory signals by docking onto high‐density lipoproteins

Abstract : The dengue virus nonstructural protein 1 (NS1) is a secreted virulence factor that modulates complement, activates immune cells and alters endothelial barriers. The molecular basis of these events remains incompletely understood. Here we describe a functional high affinity complex formed between NS1 and human high-density lipoproteins (HDL). Collapse of the soluble NS1 hexamer upon binding to the lipoprotein particle leads to the anchoring of amphipathic NS1 dimeric subunits into the HDL outer layer. The stable complex can be visualized by electron microscopy as a spherical HDL with rod-shaped NS1 dimers protruding from the surface. We further show that the assembly of NS1-HDL complexes triggers the production of pro-inflammatory cytokines in human primary macrophages while NS1 or HDL alone do not. Finally, we detect NS1 in complex with HDL and low-density lipoprotein (LDL) particles in the plasma of hospitalized dengue patients and observe NS1-apolipoprotein E-positive complexes accumulating overtime. The functional reprogramming of endogenous lipoprotein particles by NS1 as a means to exacerbate systemic inflammation during viral infection provides a new paradigm in dengue pathogenesis.
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03698274
Contributor : Stephane Petres Connect in order to contact the contributor
Submitted on : Friday, June 17, 2022 - 6:20:42 PM
Last modification on : Saturday, June 25, 2022 - 3:26:22 AM

Identifiers

Citation

Souheyla Benfrid, Kyu‐ho Park, Mariano Dellarole, James Voss, Carole Tamietti, et al.. Dengue virus NS1 protein conveys pro‐inflammatory signals by docking onto high‐density lipoproteins. EMBO Reports, EMBO Press, 2022, pp.e53600. ⟨10.15252/embr.202153600⟩. ⟨pasteur-03698274⟩

Share

Metrics

Record views

0