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

• Published in: Nature communications 2019-09, Vol.10 (1), p.1-16, Article 4430
• Main Authors: Ayala-Nunez, Nilda Vanesa, Follain, Gautier, Delalande, François, Hirschler, Aurélie, Partiot, Emma, Hale, Gillian L., Bollweg, Brigid C., Roels, Judith, Chazal, Maxime, Bakoa, Florian, Carocci, Margot, Bourdoulous, Sandrine, Faklaris, Orestis, Zaki, Sherif R., Eckly, Anita, Uring-Lambert, Béatrice, Doussau, Frédéric, Cianferani, Sarah, Carapito, Christine, Jacobs, Frank M. J., Jouvenet, Nolwenn, Goetz, Jacky G., Gaudin, Raphael
• Format: Article
• Language: English
• Subjects: 13/106; 13/31; 13/51; 14/19; 14/32; 14/63; 38/77; 42/100; 631/1647/334/1874/763; 631/326/596; 631/326/88; 631/80/304; 631/80/79; 64/116; 82/58; Adhesion; Blood vessels; Brain slice preparation; Cell adhesion; Central nervous system; Cerebellum; Embryo cells; Endothelium; Fetuses; Humanities and Social Sciences; Monocytes; multidisciplinary; Neurological diseases; Organoids; Phenotypes; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Vector-borne diseases; Viruses; Zebrafish; Zika virus
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12408-x

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. Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.