Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling
Zika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for...
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doaj-02879f123173421ca472cccc94e9d6b62020-11-25T03:37:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.582061582061Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) SignalingSandra Bos0Sandra Bos1Béatrice Poirier-Beaudouin2Valérie Seffer3Maria Manich4Cartini Mardi5Philippe Desprès6Gilles Gadea7Marie-Lise Gougeon8Institut Pasteur, Innate Immunity and Viruses Unit, Global Health Department, Paris, FranceUniversité de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, La Réunion, FranceInstitut Pasteur, Innate Immunity and Viruses Unit, Global Health Department, Paris, FranceInstitut Pasteur, Innate Immunity and Viruses Unit, Global Health Department, Paris, FranceInstitut Pasteur, Biological Image Analysis Unit, Cell Biology and Infection Department, Paris, FranceInstitut Pasteur, Innate Immunity and Viruses Unit, Global Health Department, Paris, FranceUniversité de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, La Réunion, FranceUniversité de la Réunion, INSERM U1187, CNRS UMR 9192, IRD UMR 249, Unité Mixte Processus Infectieux en Milieu Insulaire Tropical, Plateforme Technologique CYROI, La Réunion, FranceInstitut Pasteur, Innate Immunity and Viruses Unit, Global Health Department, Paris, FranceZika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions. We observed that pDCs were refractory to cell-free ZIKV virions but were effectively infected when co-cultured with ZIKV-infected cells. However, exposure of pDCs to ZIKV-infected cells resulted in limited maturation/activation with significant down regulation of CD303 expression, a severe impairment of inflammatory cytokine production, and an inability to mount an IFN-α response. We show that ZIKV developed a strategy to inhibit the IFN-α response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion.https://www.frontiersin.org/articles/10.3389/fimmu.2020.582061/fullZika virus (ZIKV)plasmacytoid dendritic cells (pDC)IFN—interferonCD303non-structural protein 1 (NS1) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sandra Bos Sandra Bos Béatrice Poirier-Beaudouin Valérie Seffer Maria Manich Cartini Mardi Philippe Desprès Gilles Gadea Marie-Lise Gougeon |
spellingShingle |
Sandra Bos Sandra Bos Béatrice Poirier-Beaudouin Valérie Seffer Maria Manich Cartini Mardi Philippe Desprès Gilles Gadea Marie-Lise Gougeon Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling Frontiers in Immunology Zika virus (ZIKV) plasmacytoid dendritic cells (pDC) IFN—interferon CD303 non-structural protein 1 (NS1) |
author_facet |
Sandra Bos Sandra Bos Béatrice Poirier-Beaudouin Valérie Seffer Maria Manich Cartini Mardi Philippe Desprès Gilles Gadea Marie-Lise Gougeon |
author_sort |
Sandra Bos |
title |
Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling |
title_short |
Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling |
title_full |
Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling |
title_fullStr |
Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling |
title_full_unstemmed |
Zika Virus Inhibits IFN-α Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling |
title_sort |
zika virus inhibits ifn-α response by human plasmacytoid dendritic cells and induces ns1-dependent triggering of cd303 (bdca-2) signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-10-01 |
description |
Zika virus (ZIKV) dramatically emerged in French Polynesia and subsequently in the Americas where it has been associated with severe neurological complications in adults and newborns, respectively. Although plasmacytoid dendritic cells (pDCs) are a key sensor of viral infection and are critical for initiating an antiviral response, little is known about the impact of ZIKV infection on pDCs. Here, we investigated the susceptibility of human pDCs to infection with multiple strains of ZIKV and further investigated the impact of infection on pDCs functions. We observed that pDCs were refractory to cell-free ZIKV virions but were effectively infected when co-cultured with ZIKV-infected cells. However, exposure of pDCs to ZIKV-infected cells resulted in limited maturation/activation with significant down regulation of CD303 expression, a severe impairment of inflammatory cytokine production, and an inability to mount an IFN-α response. We show that ZIKV developed a strategy to inhibit the IFN-α response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion. |
topic |
Zika virus (ZIKV) plasmacytoid dendritic cells (pDC) IFN—interferon CD303 non-structural protein 1 (NS1) |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.582061/full |
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