The dengue virus NS1 protein conveys pro-inflammatory signals by docking onto human high-density lipoproteins

Benfrid, S.; Park, K.-H. P.; Dellarole, M.; Voss, J. E.; Tamietti, C.; Pehau-Arnaudet, G.; Raynal, B.; Brule, S.; England, P.; Zhang, X.; Mikhailova, A.; Ungeheuer, M.-N.; Petres, S.; Biering, S.; Harris, E.; Sakuntabhai, A.; Buchy, P.; Duong, V.; Dussart, P.; Coulibaly, F.; Bontems, F.; Rey, F. A.; Flamand, M.

doi:10.1101/2021.05.05.442454

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bioRxiv · 10.1101/2021.05.05.442454

The dengue virus NS1 protein conveys pro-inflammatory signals by docking onto human high-density lipoproteins

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Abstract

The nonstructural NS1 protein is a virulence factor secreted by dengue virus (DENV)-infected cells. NS1 is known to alter the complement system, activate immune cells and perturb endothelial barriers. Here we show that pro-inflammatory signals are triggered by a high affinity complex formed between NS1 and human high-density lipoproteins (HDL). Electron microscopy images of the NS1-HDL complexes show spherical HDL particles with rod-shaped NS1 protrusions on their surface. These complexes are readily detectable in the plasma of hospitalized dengue patients using anti-apolipoprotein A-I (ApoA-I) antibodies specific of the HDL moiety. The functional reprogramming of HDL particles by the NS1 protein as a means to exacerbate systemic inflammation during DENV infection provides a new paradigm linking the human lipoprotein network to dengue pathogenesis.

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Benfrid, S., Park, K.-H. P., Dellarole, M., Voss, J. E., Tamietti, C., Pehau-Arnaudet, G., Raynal, B., Brule, S., England, P., Zhang, X., Mikhailova, A., Ungeheuer, M.-N., Petres, S., Biering, S., Harris, E., Sakuntabhai, A., Buchy, P., Duong, V., Dussart, P., Coulibaly, F., Bontems, F., Rey, F. A., Flamand, M.. 2021-05-05. The dengue virus NS1 protein conveys pro-inflammatory signals by docking onto human high-density lipoproteins. https://doi.org/10.1101/2021.05.05.442454

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