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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00389

Zika-Virus mediated death of hippocampal neurons is independent from maturation state

Caroline Buettner1, Maxi Heer1,  Jasmin Traichel1,  Martin Schwemmle1 and  Bernd Heimrich2*
  • 1Faculty of Medicine, Institute of Anatomy & Cell Biology, Dept. Neuroanatomy, University of Freiburg, Germany
  • 2Faculty of Medicine, University of Freiburg, Germany

Zika virus (ZIKV) infection of pregnant women and diaplazental transmission to the fetus is linked to the congenital syndrome of microcephaly in newborns. This neuropathology is believed to result from significant death of neuronal progenitor cells. Here we examined the fate of neurons in the developing hippocampus, a brain structure which houses neuronal populations of different maturation states. For this purpose, we infected hippocampal slice cultures from immunocompetent newborn mice with ZIKV and monitored changes in hippocampal architecture. In neurons of all hippocampal subfields ZIKV was detected by immunofluorescence labeling and electron microscopy. This includes pyramidal neurons that maturate during the embryonic phase. In the dentate gyrus, ZIKV could be found in the Cajal-Retzius cells which belong to the earliest born cortical neurons, but also in granule cells that are predominantly generated postnatally. Intriguingly, virus particles were also present in the correctly outgrowing mossy fiber axons of juvenile granule cells, suggesting that viral infection does not impair region- and layer-specific formation of this projection. ZIKV infection of hippocampal tissue was accompanied by both a profound astrocyte indicating tissue injury and a microglia response suggesting phagocytotic activity.Furthermore, depending on the viral load and incubation time, we observed extensive overall neuronal loss in the cultured hippocampal slice cultures. Thus, we conclude ZIKV can replicate in various neuronal populations and trigger neuronal death independent of the maturation state of infected cells.

Keywords: Zika virus, Hippocampus & Amygdala, Cell Death, organotypic slice culture, Electron microscope analysis

Received: 24 Jan 2019; Accepted: 06 Aug 2019.

Edited by:

Oliver Von Bohlen Und Halbach, Universitätsmedizin Greifswald, Germany

Reviewed by:

Gonzalo Alvarez-Bolado, Heidelberg University, Germany
Alexander Drakew, Institute of Clinical Neuranatomy, Goethe University Frankfurt, Germany  

Copyright: © 2019 Buettner, Heer, Traichel, Schwemmle and Heimrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Bernd Heimrich, Faculty of Medicine, University of Freiburg, Freiburg, Germany,