Neural Stem Cell Tropism of Zika Virus

The Zika virus outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV), can cause encephalitis but were not demonstrated to cause microcephaly. It remained unclear whether Zika virus (ZIKV) and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. In collaboration with the group of Nathalie Pardigon at institut Pasteur, we developed an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4) (Brault et al, EBioMed, 2016). We showed that this tissue was able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis revealed a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displayed a very different tropism of infection, with a bias towards neurons. We further showed that ZIKV infection, but not WNV infection, impaired cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work established a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and revealed specific preferential infection of neural stem cells by ZIKV.

ZIKV infects RG progenitors preferentially. E16 mouse cortical slice infected with Zika virus (ZIKV) shows preferential infection of the elongated RG cells.
Image belongs to Team BAFFET

Brault JB, Khou C, Basset J, Coquand L, …, Pardigon N, Baffet AD. (2016) Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex. EBioMedicine 10, 71-76.