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

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.

SUBMITTER: Ayala-Nunez NV

PROVIDER: S-EPMC6764950 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Ayala-Nunez Nilda Vanesa NV Follain Gautier G Delalande François F Hirschler Aurélie A Partiot Emma E Hale Gillian L GL Bollweg Brigid C BC Roels Judith J Chazal Maxime M Bakoa Florian F Carocci Margot M Bourdoulous Sandrine S Faklaris Orestis O Zaki Sherif R SR Eckly Anita A Uring-Lambert Béatrice B Doussau Frédéric F Cianferani Sarah S Carapito Christine C Jacobs Frank M J FMJ Jouvenet Nolwenn N Goetz Jacky G JG Gaudin Raphael R

Nature communications 20190927 1

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 b ...[more]

PMID: 31562326

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Project description:We investigated the hypothesis that transmigration drives monocyte transcriptional changes. Using Agilent Whole Human Genome Microarrays, we identified over 600 differentially expressed genes (2x, p<0.05) in freshly isolated human monocytes following 1.5 h of transmigration across IL1beta-stimulated ECs compared to untreated monocytes. Genes up-regulated by monocyte transmigration belong to a number of overrepresented functional groups including immune response, and inhibition of apoptosis. qRT-PCR confirmed increased expression of monocyte chemotactic proteins 1 and 3 and of NLR family apoptosis inhibitory protein (NAIP) following monocyte transmigration. In addition, quantification of annexin V binding revealed a reduction in apoptosis following monocyte transmigration. Comparison of gene expression in transmigrated monocytes to additional controls (monocytes which failed to transmigrate and monocytes incubated beneath stimulated ECs) revealed 89 differentially expressed genes which were controlled by the physical process of diapedesis. Functional annotation of these genes showed down-regulation of antimicrobial genes (e.g. alpha-defensin down 50x, cathelicidin down 9x, and cathepsin G down 3x). qRT-PCR confirmed down-regulation of these genes. Immunoblots confirmed that monocyte transmigration down-regulates alpha-defensin protein expression. Overall, these data indicate that exposure of monocytes to stimulated ECs promotes further monocyte recruitment and inhibits monocyte apoptosis. Unexpectedly, following transmigration monocytes displayed reduced anti-microbial expression. Monocytes were allowed to transmigrate across IL1b stimulated HUVEC. Monocytes which transmigrated and monocytes which failed to transmigrate were collected after 1.5 hours from 3 experimental replicates of different human donors. Untreated monocytes were collected as a control from 4 human donors. Monocytes incubated beneath stimulated HUVEC for 1.5 hours were also collected from four human donors as a control.

Dataset Information

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

Publications

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

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