BACKGROUND: The recent Zika virus (ZIKV) outbreak has linked ZIKV with microcephaly and other central nervous system pathologies in humans. Astrocytes are among the first cells to respond to ZIKV infection in the brain and are also targets for virus infection. In this study, we investigated the interaction between ZIKV and primary human brain cortical astrocytes (HBCA). RESULTS: HBCAs were highly sensitive to representatives of both Asian and African ZIKV lineages and produced high viral yields. The infection was associated with limited immune cytokine/chemokine response activation; the highest increase of expression, following infection, was seen in CXCL-10 (IP-10), interleukin-6, 8, 12, and CCL5 (RANTES). Ultrastructural changes in the ZIKV-infected HBCA were characterized by electron tomography (ET). ET reconstructions elucidated high-resolution 3D images of the proliferating and extensively rearranged endoplasmic reticulum (ER) containing viral particles and virus-induced vesicles, tightly juxtaposed to collapsed ER cisternae. CONCLUSIONS: The results confirm that human astrocytes are sensitive to ZIKV infection and could be a source of proinflammatory cytokines in the ZIKV-infected brain tissue.

Department of Virology Veterinary Research Institute Hudcova 70 62100 Brno Czech Republic

EHESP French School of Public Health IRD French Institute of Research for Development EPV UMR_D 190 Emergence des Pathologies Virales Aix Marseille Université Marseille France

Faculty of Science University of South Bohemia Branisovska 31 37005 Ceske Budejovice Czech Republic

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Branisovska 31 37005 Ceske Budejovice Czech Republic

Laboratory of Molecular Evolution and Bioinformatics Department of Microbiology Institute of Microbiology Sciences University of São Paulo São Paulo 05508 000 Brazil

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