Dengue virus NS1 protein conveys pro-inflammatory signals by docking onto high-density lipoproteins.
Arbovirus
accessory protein
hemorrhagic fever
lipoprotein particle
molecular pathogenesis
virulence factor
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 07 2022
05 07 2022
Historique:
revised:
24
04
2022
received:
10
07
2021
accepted:
27
04
2022
pubmed:
25
5
2022
medline:
8
7
2022
entrez:
24
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35607830
doi: 10.15252/embr.202153600
pmc: PMC10549233
doi:
Substances chimiques
Lipoproteins, HDL
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e53600Subventions
Organisme : NIAID NIH HHS
ID : R01 AI124493
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI146464
Pays : United States
Informations de copyright
© 2022 The Authors.
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