1. Zika Virus Inhibits IFN-a Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling
- Author
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Valérie Seffer, Cartini Mardi, Marie-Lise Gougeon, Gilles Gadea, Béatrice Poirier-Beaudouin, Maria Manich, Philippe Desprès, Sandra Bos, Univ, Réunion, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Immunité Innée - Innate Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by Institut Pasteur and the POE FEDER 2014-20 of the Conseil Régional de La Reunion (ZIKAlert program, N° SYNERGIE RE00001902) and by the INCEPTION project (PIA/ANR-16-CONV-0005). SB was supported by a PhD grant from MEESR (Ecole Doctorale STS, Université de La Réunion)., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-IRD-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,medicine.medical_treatment ,plasmacytoid dendritic cells (pDC) ,Immunology ,Down-Regulation ,Biology ,Viral infection ,Cell Line ,Zika virus ,Zika virus (ZIKV) ,non-structural protein 1 (NS1) ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,Chlorocebus aethiops ,ZikV Infection ,medicine ,Animals ,Humans ,Immunology and Allergy ,Lectins, C-Type ,Receptors, Immunologic ,Vero Cells ,Original Research ,Inflammation ,Membrane Glycoproteins ,Zika Virus Infection ,Interferon-alpha ,hemic and immune systems ,IFN-interferon ,Dendritic Cells ,Zika Virus ,biology.organism_classification ,Virology ,3. Good health ,030104 developmental biology ,Cytokine ,CD303 ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,IFN—interferon ,Cytokines ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,lcsh:RC581-607 ,Signal Transduction ,030215 immunology - Abstract
International audience; 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-a response. We show that ZIKV developed a strategy to inhibit the IFN-a response in primary human pDCs likely mediated through NS1-dependent CD303 signaling, thus suggesting a new mechanism of immune evasion.
- Published
- 2020