Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

Lebeau, Grégorie; Lagrave, Alisé; Ogire, Eva; Grondin, Lauriane; S, Seriacaroupin; Moutoussamy, Cédric; Mavingui, Patrick; Hoarau, Jean-Jacques; Roche, Marjolaine; Krejbich-Trotot, Pascale; Desprès, Philippe; Viranaïcken, Wildriss

doi:10.3390/vaccines9090946

Cited by 12 publications

(5 citation statements)

References 57 publications

(96 reference statements)

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“…In addition, human antibodies targeting ZIKV-NS1 protect against disease development in a mouse model [ 82 ]. Thus, recombinant ZIKV-NS1 and DENV2-NS1 proteins would be considered as targets of choice for vaccine development [ 81 , 83 ]. Thanks to our work, we have available cell lines that stably overexpress and secrete these two NS1s.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection

Safadi

Lebeau

Lagrave

et al. 2023

Viruses

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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, and infectious and pathophysiological processes. Some viruses are known to hijack the cell production and content of EVs for their benefit. Here, we investigate whether two pathogenic flaviviruses i.e., Zika Virus (ZIKV) and Dengue virus (DENV2) could have an impact on the features of EVs. The analysis of EVs produced by infected cells allowed us to identify that the non-structural protein 1 (NS1), described as a viral toxin, is 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.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection

Safadi

Lebeau

Lagrave

et al. 2023

Viruses

View full text Add to dashboard Cite

show abstract

“…In addition, human antibodies targeting ZIKV-NS1 protect against disease development in a mouse model [77]. Thus, recombinant ZIKV-NS1 and DENV2-NS1 proteins would be considered as targets of choice for vaccine development [76,78]. Thanks to our work, we have available cell lines that stably overexpress and secrete these two NS1s.…”

Section: Discussionmentioning

confidence: 96%

Extracellular Vesicles are Conveyors of the NS1 Toxin during Flavivirus Infection

SAFADI¹,

LEBEAU²,

LAGRAVE³

et al. 2022

Preprint

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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.

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“…GG performed better than the positive control CQ which only inhibited DV1-3. Lower viral loads and lower NS1 antigen levels reduce the risk of developing severe dengue [8,12]. MNTD (166.67 µg/mL) of the aqueous extract of GG inhibited all four dengue serotypes in Vero cells at a magnitude of two.…”

Section: Discussionmentioning

confidence: 99%

“…Bioassay guided fractionation of the aqueous extract of GG resulted in the isolation of fractions E and F, but only dengue serotypes 1 and 4 were significantly inhibited by these fractions. NS1 antigen has been found to be significantly associated with severe dengue infections [12]. Since aqueous extract of GG roots was found to be a better inhibitor of all four serotypes, further evaluation was carried out with dengue virus infected monocytes to determine its effects on NS1 antigen production.…”

Section: Introductionmentioning

confidence: 99%

Anti-dengue viral activity of Glycyrrhiza glabra roots in Vero cells

Jayasekera,

Suresh,

Goonasekera

et al. 2023

Preprint

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Dengue is a global public health problem but no antiviral agent exists for dengue. Plants have been the source of many pharmaceutical agents. Therefore, we explored the antiviral potential of the aqueous extracts of Glycyrrhiza glabra (GG) roots on dengue viruses. Cell cytotoxicity assay with 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide solution was used for estimating the maximum nontoxic dose (MNTD) and 50% cytotoxic concentration (CC50). Plaque reduction antiviral assay on Vero cells infected with dengue virus serotypes 1,2,3 and 4 were treated with dilutions of the MNTD of GG extract to calculate the half maximal inhibitory concentration (IC50). Selectivity index (SI) was calculated as CC50/IC50 ratio. Following bioactivity guided fractionation, MNTD, CC50, IC50 and SI values for fractions E and F were similarly obtained. Inhibition of NS1 antigen levels produced by dengue serotype-1 infected monocytes was studied in the presence and absence of GG extract after 48 hours. GG MNTD and CC50 were 166.7 µg/mL and 651.9 µg/mL. GG extract showed 98-100% inhibition of all four dengue serotypes at the MNTD and the IC50 values of the four serotypes ranged from 10-50 µg/mL indicating moderate pan-serotype inhibitory activity. Cytotoxicity of GG against Vero cells was low (CC50 >500 µg/mL). SI of GG extract for all four dengue serotypes were >10, indicating it had good potential as an antiviral agent. Fraction E and F had low to moderate inhibitory activity for all four serotypes and showed good potential as an antiviral agent only for dengue 4. This is the first report of significant anti-dengue viral activity of GG extract on all four dengue serotypes.

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Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

Cited by 12 publications

References 57 publications

Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection

Extracellular Vesicles Are Conveyors of the NS1 Toxin during Dengue Virus and Zika Virus Infection

Extracellular Vesicles are Conveyors of the NS1 Toxin during Flavivirus Infection

Anti-dengue viral activity of Glycyrrhiza glabra roots in Vero cells

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