Characterisation of Zika virus infection in primary human astrocytes

Abstract\ud \ud Background\ud 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).\ud \ud \ud Results\ud 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.\ud \ud \ud Conclusions\ud 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.This work was supported by the Czech Science Foundation (Grants 16-20054S and 17-02196S); the Ministry of Education, Youth, and Sports of the Czech Republic, under the NPU I program (Grant LO1218); by Project “FIT” (Pharmacology, Immunotherapy, nanoToxicology), which was funded by the European Regional Development Fund; the National Subvention for the Development of Research Organizations (Grant RVO: 61388963); and the European Virus Archive Goes Global project, which has received funding from the European Union’s Horizon 2020 research and innovation program (Grant 653316). The Laboratory of EM supported by the Ministry of Education, Youth, and Sports of the Czech Republic (LM2015062 Czech-BioImaging) and Technology Agency of the Czech Republic (TE01020118)