Skip to Main content Skip to Navigation
Journal articles

Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein.

Abstract : Dengue virus (DENV) causes the major arboviral disease of the tropics, characterized in its severe forms by signs of hemorrhage and plasma leakage. DENV encodes a nonstructural glycoprotein, NS1, that associates with intracellular membranes and the cell surface. NS1 is eventually secreted as a soluble hexamer from DENV-infected cells and circulates in the bloodstream of infected patients. Extracellular NS1 has been shown to modulate the complement system and to enhance DENV infection, yet its structure and function remain essentially unknown. By combining cryoelectron microscopy analysis with a characterization of NS1 amphipathic properties, we show that the secreted NS1 hexamer forms a lipoprotein particle with an open-barrel protein shell and a prominent central channel rich in lipids. Biochemical and NMR analyses of the NS1 lipid cargo reveal the presence of triglycerides, bound at an equimolar ratio to the NS1 protomer, as well as cholesteryl esters and phospholipids, a composition evocative of the plasma lipoproteins involved in vascular homeostasis. This study suggests that DENV NS1, by mimicking or hijacking lipid metabolic pathways, contributes to endothelium dysfunction, a key feature of severe dengue disease.
Document type :
Journal articles
Complete list of metadatas

Cited literature [54 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-00590815
Contributor : Mireille Gau <>
Submitted on : Monday, April 23, 2018 - 10:32:44 AM
Last modification on : Monday, June 22, 2020 - 12:08:08 PM
Long-term archiving on: : Wednesday, September 19, 2018 - 2:22:29 AM

File

PNAS_merged_file_25Nov10.pdf
Files produced by the author(s)

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

Citation

Irina Gutsche, Fasséli Coulibaly, James E Voss, Jérôme Salmon, Jacques d'Alayer, et al.. Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2011, 108 (19), pp.8003-8008. ⟨10.1073/pnas.1017338108⟩. ⟨pasteur-00590815⟩

Share

Metrics

Record views

1730

Files downloads

811