Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway
Zika virus (ZIKV) is a mosquito-borne Flavivirus that causes Zika disease with particular neurological complications, including Guillain-Barré Syndrome and congenital microcephaly. Although ZIKV has been shown to directly infect human neural progenitor cells (hNPCs), thereby decreasing their viabil...
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| Format: | Article |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1637283 |
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| author | Pauline Ferraris Marielle Cochet Rodolphe Hamel Ivan Gladwyn-Ng Christian Alfano Fodé Diop Déborah Garcia Loïc Talignani Claudia N. Montero-Menei Antoine Nougairède Hans Yssel Laurent Nguyen Muriel Coulpier Dorothée Missé |
| author_facet | Pauline Ferraris Marielle Cochet Rodolphe Hamel Ivan Gladwyn-Ng Christian Alfano Fodé Diop Déborah Garcia Loïc Talignani Claudia N. Montero-Menei Antoine Nougairède Hans Yssel Laurent Nguyen Muriel Coulpier Dorothée Missé |
| author_sort | Pauline Ferraris |
| collection | DOAJ |
| description | Zika virus (ZIKV) is a mosquito-borne Flavivirus that causes Zika disease with particular neurological complications, including Guillain-Barré Syndrome and congenital microcephaly. Although ZIKV has been shown to directly infect human neural progenitor cells (hNPCs), thereby decreasing their viability and growth, it is as yet unknown which of the cellular pathways involved in the disruption of neurogenesis are affected following ZIKV infection. By comparing the effect of two ZIKV strains in vitro on hNPCs, the differentiation process of the latter cells was found to lead to a decreased susceptibility to infection and cell death induced by each of the ZIKV strains, which was associated with an earlier and stronger antiviral innate immune response in infected, differentiated hNPCs, as compared to undifferentiated cells. Moreover, ZIKV modulated, both in hNPCs and in vivo in fetal brain in an experimental mouse model, the expression of the Notch pathway which is involved in cellular proliferation, apoptosis and differentiation during neurogenesis. These results show that the differentiation state of hNPCs is a significant factor contributing to the outcome of ZIKV infection and furthermore suggest that ZIKV infection might initiate early activation of the Notch pathway resulting in an abnormal differentiation process, implicated in ZIKV-induced brain injury. |
| format | Article |
| id | doaj-art-b90e38ced74e4ed9b125ceb78efae4da |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-b90e38ced74e4ed9b125ceb78efae4da2025-08-20T01:54:16ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811003101610.1080/22221751.2019.1637283Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathwayPauline Ferraris0Marielle Cochet1Rodolphe Hamel2Ivan Gladwyn-Ng3Christian Alfano4Fodé Diop5Déborah Garcia6Loïc Talignani7Claudia N. Montero-Menei8Antoine Nougairède9Hans Yssel10Laurent Nguyen11Muriel Coulpier12Dorothée Missé13MIVEGEC, IRD, Univ. Montpellier, CNRS, Montpellier, FranceUMR1161 Virologie, ANSES, INRA, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, FranceMIVEGEC, IRD, Univ. Montpellier, CNRS, Montpellier, FranceGIGA-Neuroscience, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège, BelgiumGIGA-Neuroscience, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège, BelgiumMIVEGEC, IRD, Univ. Montpellier, CNRS, Montpellier, FranceMIVEGEC, IRD, Univ. Montpellier, CNRS, Montpellier, FranceMIVEGEC, IRD, Univ. Montpellier, CNRS, Montpellier, FranceCRCINA, INSERM, Université de Nantes, Université d’Angers, Angers, FranceUVE, Aix Marseille Univ-IRD 190, Inserm 1207-IHU Méditerranée Infection, Marseille, FranceCentre d’Immunologie et des Maladies Infectieuses, Inserm, U1135, Sorbonne Universités, UPMC, APHP Hôpital Pitié-Salpêtrière, Paris, FranceGIGA-Neuroscience, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, C.H.U. Sart Tilman, Liège, BelgiumUMR1161 Virologie, ANSES, INRA, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, FranceMIVEGEC, IRD, Univ. Montpellier, CNRS, Montpellier, FranceZika virus (ZIKV) is a mosquito-borne Flavivirus that causes Zika disease with particular neurological complications, including Guillain-Barré Syndrome and congenital microcephaly. Although ZIKV has been shown to directly infect human neural progenitor cells (hNPCs), thereby decreasing their viability and growth, it is as yet unknown which of the cellular pathways involved in the disruption of neurogenesis are affected following ZIKV infection. By comparing the effect of two ZIKV strains in vitro on hNPCs, the differentiation process of the latter cells was found to lead to a decreased susceptibility to infection and cell death induced by each of the ZIKV strains, which was associated with an earlier and stronger antiviral innate immune response in infected, differentiated hNPCs, as compared to undifferentiated cells. Moreover, ZIKV modulated, both in hNPCs and in vivo in fetal brain in an experimental mouse model, the expression of the Notch pathway which is involved in cellular proliferation, apoptosis and differentiation during neurogenesis. These results show that the differentiation state of hNPCs is a significant factor contributing to the outcome of ZIKV infection and furthermore suggest that ZIKV infection might initiate early activation of the Notch pathway resulting in an abnormal differentiation process, implicated in ZIKV-induced brain injury.https://www.tandfonline.com/doi/10.1080/22221751.2019.1637283Zikaarbovirushuman neural progenitorNotchneurogenesisflavivirus |
| spellingShingle | Pauline Ferraris Marielle Cochet Rodolphe Hamel Ivan Gladwyn-Ng Christian Alfano Fodé Diop Déborah Garcia Loïc Talignani Claudia N. Montero-Menei Antoine Nougairède Hans Yssel Laurent Nguyen Muriel Coulpier Dorothée Missé Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway Emerging Microbes and Infections Zika arbovirus human neural progenitor Notch neurogenesis flavivirus |
| title | Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway |
| title_full | Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway |
| title_fullStr | Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway |
| title_full_unstemmed | Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway |
| title_short | Zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the Notch pathway |
| title_sort | zika virus differentially infects human neural progenitor cells according to their state of differentiation and dysregulates neurogenesis through the notch pathway |
| topic | Zika arbovirus human neural progenitor Notch neurogenesis flavivirus |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1637283 |
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