title: Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex.
abstract: The recent Zika 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 remains unclear whether Zika virus (ZIKV) and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4). We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Brault
authors.affiliation: Institut Pasteur, ERI/CIBU Arbovirus Group, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Khou
authors.affiliation: Institut Pasteur, ERI/CIBU Arbovirus Group, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Justine
authors.initials: J
authors.lastname: Basset
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Coquand
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fraisier
authors.affiliation: Institut Pasteur, ERI/CIBU Arbovirus Group, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Frenkiel
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.affiliation: Institut Pasteur, ERI/CIBU Arbovirus Group, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Manuguerra
authors.affiliation: Institut Pasteur, ERI/CIBU Arbovirus Group, 25 rue du Dr Roux, 75015 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pardigon
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR144, F-75005 Paris, France. Electronic address: alexandre.baffet@curie.fr.
authors.forename: Alexandre D
authors.initials: AD
authors.lastname: Baffet
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D004195:Disease Models, Animal; D005416:Flavivirus / Q000145:classification / Q000502:physiology*; D051379:Mice; D019579:Neocortex / Q000166:cytology* / Q000821:virology*; D058953:Neural Stem Cells / Q000821:virology*; D010802:Phylogeny; D014709:Vero Cells; D056189:Viral Tropism; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000821:virology*