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

Nilda Vanesa Ayala-Nunez (1, 2, 3) , Gautier Follain (4, 5) , Francois Delalande (6) , Aurélie Hirschler (6) , Emma Partiot (1) , Gillian Hale (7) , Brigid Bollweg (7) , Judith Roels (8) , Maxime Chazal (9) , Florian Bakoa (9) , Margot M. Carocci (2) , Sandrine Bourdoulous (10, 11) , Orestis Faklaris (12) , Sherif Zaki (7) , Anita Eckly (13, 2) , Béatrice Uring-Lambert (14) , Frédéric Doussau (15) , Sarah Cianférani (6) , Christine Carapito (6) , Frank Jacobs (8) , Nolwenn Jouvenet (9) , Jacky Goetz (4, 5) , Raphael Gaudin (1, 2)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 UNISTRA - Université de Strasbourg
3 INSERM - Institut National de la Santé et de la Recherche Médicale
4 IRM - Immuno-Rhumatologie Moléculaire
5 FMTS - Fédération de Médecine Translationnelle de Strasbourg
6 DSA-IPHC - Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires
7 CDC - Centers for Disease Control and Prevention [Atlanta]
8 Swammerdam Institute for Life Sciences
9 Génomique virale et vaccination
10 UPD5 - Université Paris Descartes - Paris 5
11 IC UM3 (UMR 8104 / U1016) - Institut Cochin
12 BCM - BioCampus
13 Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion
14 HUS - Les Hôpitaux Universitaires de Strasbourg
15 INCI - Institut des Neurosciences Cellulaires et Intégratives

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.

Domaines: Virologie

Nilda Vanesa Ayala-Nunez, Gautier Follain, Francois Delalande, Aurélie Hirschler, Emma Partiot, et al.. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells. Nature Communications, 2019, 10 (1), pp.4430. ⟨10.1038/s41467-019-12408⟩. ⟨hal-02327473⟩