Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Extracellular Vesicles are Conveyors of the NS1 Toxin during Flavivirus Infection

Daed EL SAFADI
,
Grégorie LEBEAU
,
Alisé LAGRAVE
,
Julien Mélade
ORCID logo ,
Lauriane GRONDIN
,
Sarah ROSANALY
,
Floran Begue
,
Mathilde Hoareau
,
Bryan Veeren
ORCID logo ,
Marjolaine ROCHE
,
Jean-jacques Hoarau
ORCID logo ,
Olivier Meilhac
,
Patrick Mavingui
,
Philippe DESPRES
ORCID logo ,
Wildriss VIRANAICKEN
* ORCID logo ,
Pascale KREJBICH-TROTOT
* ORCID logo
Version 1 : Received: 22 December 2022 / Approved: 26 December 2022 / Online: 26 December 2022 (03:37:59 CET)

A peer-reviewed article of this Preprint also exists.

Safadi, D.E.; Lebeau, G.; Lagrave, A.; Mélade, J.; Grondin, L.; Rosanaly, S.; Begue, F.; Hoareau, M.; Veeren, B.; Roche, M.; Hoarau, J.-J.; Meilhac, O.; Mavingui, P.; Desprès, P.; Viranaïcken, W.; Krejbich-Trotot, P. Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection. Viruses 2023, 15, 364. Safadi, D.E.; Lebeau, G.; Lagrave, A.; Mélade, J.; Grondin, L.; Rosanaly, S.; Begue, F.; Hoareau, M.; Veeren, B.; Roche, M.; Hoarau, J.-J.; Meilhac, O.; Mavingui, P.; Desprès, P.; Viranaïcken, W.; Krejbich-Trotot, P. Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection. Viruses 2023, 15, 364.

Abstract

Extracellular vesicles (EVs), produced during viral infections, are of emerging interest in understanding infectious processes and host-pathogen interactions. EVs and exosomes in particular have the natural ability to transport nucleic acids, proteins, and other components of cellular or viral origin. Thus, they participate in intercellular communication, immune responses, infectious and pathophysiological processes. Some viruses are known to hijack the cell production and content of EVs for their benefit. Here, we investigated whether two pathogenic flaviviruses i.e. Zika Virus (ZIKV) and Dengue virus (DENV2) could have an impact on the features of EVs. Analysis of EVs produced by infected cells allowed us to identify that the non-structural protein 1 (NS1), described as a viral toxin, was associated with exosomes. This observation could be confirmed under conditions of overexpression of recombinant NS1 from each flavivirus. Using different isolation methods (i.e. exosome isolation kit, size exclusion chromatography, Polyethylene Glycol enrichment, and ELISA capture), we showed that NS1 was present as a dimer at the surface of excreted exosomes and that this association could occur in the extracellular compartment. This finding could be of major importance in a physiological context. Indeed, this capacity of NS1 to address EVs and its implication in the pathophysiology during Dengue or Zika diseases should be explored. Furthermore, exosomes that have demonstrated a natural capacity to vectorize NS1 could serve as useful tools for vaccine development.

Keywords

Flavivirus; Dengue; Zika; NS1; exosome; viral toxin vectorization

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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