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© Pierre Gounon
Virus influenza purifié, agent de la grippe. Ce virus enveloppé possède un génome fragmenté : 8 segments d'ARN négatif protégés par une nucléocapside.
Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
01
Jan 2016
Ending Date
30
Sep 2017
Status
Completed
Members
3
Structures
3
Publications
1

About

Neurotropic flaviviruses are human pathogens responsible for numerous viral encephalitic diseases. West Nile and Japanese encephalitis flaviviruses infect the adult brain and are also responsible for congenital infections that impact fetal brain development. Zika virus is also a neurotropic flavivirus but seems rarely responsible for neurological diseases in adults. However, Zika virus infection was recently linked to microcephaly, a disease causing devastating congenital disorders and characterized by a reduced size of the cerebral cortex which is due to reduced neurogenesis or increased cell death. The mechanisms by which specific cell types may be infected in the developing neocortex by Zika virus and what the consequences of infection may be on its development are under intense scrutiny.

In order to address these questions, we have developed an assay to infect mouse E15 embryonic brain slices and performed infections with West Nile virus, Zika virus and dengue virus type 4. We showed that mouse neocortex is able to support viral replication of Zika and West Nile viruses, but not of the non-neurotropic dengue 4 virus. We also showed that while West Nile virus shows a preferential tropism of infection for neurons, Zika virus infection was strongly biased towards the neural stem cells. Furthermore, we found that Zika virus, but not West Nile virus, was able to impair cell cycle.

We are now investigating whether Zika virus can induce apoptosis in neural progenitor cells. Using a molecular virology approach, we will try to identify viral determinants causing Zika virus pathogenicity.

This work will be done in collaboration with Institut Curie.

Fundings