PUBLICATION
A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis
- Authors
- Sow, A.A., Jamadagni, P., Scaturro, P., Patten, S.A., Chatel-Chaix, L.
- ID
- ZDB-PUB-241203-4
- Date
- 2024
- Source
- PLoS pathogens 20: e1012756e1012756 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Zebrafish*
- Brain/metabolism
- Brain/pathology
- Brain/virology
- Neurons/metabolism
- Neurons/pathology
- Neurons/virology
- Neural Stem Cells/metabolism
- Neural Stem Cells/pathology
- Neural Stem Cells/virology
- Disease Models, Animal*
- Humans
- Neurogenesis/physiology
- Zika Virus*/physiology
- Zika Virus Infection*/metabolism
- Zika Virus Infection*/pathology
- Zika Virus Infection*/virology
- Viral Nonstructural Proteins/genetics
- Viral Nonstructural Proteins/metabolism
- PubMed
- 39621753 Full text @ PLoS Pathog.
Citation
Sow, A.A., Jamadagni, P., Scaturro, P., Patten, S.A., Chatel-Chaix, L. (2024) A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis. PLoS pathogens. 20:e1012756e1012756.
Abstract
Infection of pregnant women by Zika virus (ZIKV) is associated with severe neurodevelopmental defects in newborns through poorly defined mechanisms. Here, we established a zebrafish in vivo model of ZIKV infection to circumvent limitations of existing mammalian models. Leveraging the unique tractability of this system, we gained unprecedented access to the ZIKV-infected brain at early developmental stages. The infection of zebrafish larvae with ZIKV phenocopied the disease in mammals including a reduced head area and neural progenitor cells (NPC) infection and depletion. Moreover, transcriptomic analyses of NPCs isolated from ZIKV-infected embryos revealed a distinct dysregulation of genes involved in survival and neuronal differentiation, including downregulation of the expression of the glutamate transporter vglut1, resulting in an altered glutamatergic network in the brain. Mechanistically, ectopic expression of ZIKV protein NS4A in the larvae recapitulated the morphological defects observed in infected animals, identifying NS4A as a key determinant of neurovirulence and a promising antiviral target for developing therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping