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Nat Commun. 2019 Sep 27;10(1):4430. doi: 10.1038/s41467-019-12408-x.

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

Author information

1
Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS, Université de Montpellier, 34293, Montpellier, France.
2
Université de Strasbourg, INSERM, 67000, Strasbourg, France.
3
INSERM U1109 and FMTS, 67000, Strasbourg, France.
4
Laboratoire de Spectrométrie de Masse Bio-Organique, IPHC, UMR 7178, CNRS-Université de Strasbourg, ECPM, 67087, Strasbourg, France.
5
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS: G32, Atlanta, GA, 30329-4027, USA.
6
University of Amsterdam, Swammerdam Institute for Life Sciences, Science Park 904, 1098XH, Amsterdam, The Netherlands.
7
Viral Genomics and Vaccination Unit, UMR3569 CNRS, Virology Department, Institut Pasteur, 75015, Paris, France.
8
Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS, 67000, Strasbourg, France.
9
INSERM U1016, Institut Cochin, CNRS UMR8104, Université Paris Descartes, Paris, France.
10
MRI Core facility, Biocampus, CNRS UMS 3426, 34293, Montpellier, France.
11
Hôpitaux universitaires de Strasbourg, laboratoire central d'immunologie, 67000, Strasbourg, France.
12
Institut des Neurosciences Cellulaires et Intégratives, CNRS, Université de Strasbourg, 67000, Strasbourg, France.
13
Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS, Université de Montpellier, 34293, Montpellier, France. raphael.gaudin@irim.cnrs.fr.
14
Université de Strasbourg, INSERM, 67000, Strasbourg, France. raphael.gaudin@irim.cnrs.fr.

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.

PMID:
31562326
PMCID:
PMC6764950
DOI:
10.1038/s41467-019-12408-x
[Indexed for MEDLINE]
Free PMC Article

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