Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells

Nilda Vanesa Ayala-Nunez, Gautier Follain, François Delalande, Aurélie Hirschler, Emma Partiot, Gillian L. Hale, Brigid C. Bollweg, Judith Roels, Maxime Chazal, Florian Bakoa, Margot Carocci, Sandrine Bourdoulous, Orestis Faklaris, Sherif R. Zaki, Anita Eckly, Béatrice Uring-Lambert, Frédéric Doussau, Sarah Cianferani, Christine Carapito, Frank M. J. Jacobs, Nolwenn Jouvenet, Jacky G. Goetz and Raphael Gaudin ()
Additional contact information
Nilda Vanesa Ayala-Nunez: Université de Montpellier
Gautier Follain: INSERM U1109 and FMTS
François Delalande: CNRS-Université de Strasbourg, ECPM
Aurélie Hirschler: CNRS-Université de Strasbourg, ECPM
Emma Partiot: Université de Montpellier
Gillian L. Hale: Centers for Disease Control and Prevention
Brigid C. Bollweg: Centers for Disease Control and Prevention
Judith Roels: University of Amsterdam, Swammerdam Institute for Life Sciences
Maxime Chazal: Institut Pasteur
Florian Bakoa: Institut Pasteur
Margot Carocci: Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS
Sandrine Bourdoulous: Université Paris Descartes
Orestis Faklaris: MRI Core facility, Biocampus
Sherif R. Zaki: Centers for Disease Control and Prevention
Anita Eckly: Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS
Béatrice Uring-Lambert: laboratoire central d’immunologie
Frédéric Doussau: Université de Strasbourg
Sarah Cianferani: CNRS-Université de Strasbourg, ECPM
Christine Carapito: CNRS-Université de Strasbourg, ECPM
Frank M. J. Jacobs: University of Amsterdam, Swammerdam Institute for Life Sciences
Nolwenn Jouvenet: Institut Pasteur
Jacky G. Goetz: INSERM U1109 and FMTS
Raphael Gaudin: Université de Montpellier

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention.

Date: 2019
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DOI: 10.1038/s41467-019-12408-x

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