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Aberrant NAD + metabolism underlies Zika virus-induced microcephaly.
- Source :
-
Nature metabolism [Nat Metab] 2021 Aug; Vol. 3 (8), pp. 1109-1124. Date of Electronic Publication: 2021 Aug 12. - Publication Year :
- 2021
-
Abstract
- Zika virus (ZIKV) infection during pregnancy can cause microcephaly in newborns, yet the underlying mechanisms remain largely unexplored. Here, we reveal extensive and large-scale metabolic reprogramming events in ZIKV-infected mouse brains by performing a multi-omics study comprising transcriptomics, proteomics, phosphoproteomics and metabolomics approaches. Our proteomics and metabolomics analyses uncover dramatic alteration of nicotinamide adenine dinucleotide (NAD <superscript>+</superscript> )-related metabolic pathways, including oxidative phosphorylation, TCA cycle and tryptophan metabolism. Phosphoproteomics analysis indicates that MAPK and cyclic GMP-protein kinase G signaling may be associated with ZIKV-induced microcephaly. Notably, we demonstrate the utility of our rich multi-omics datasets with follow-up in vivo experiments, which confirm that boosting NAD <superscript>+</superscript> by NAD <superscript>+</superscript> or nicotinamide riboside supplementation alleviates cell death and increases cortex thickness in ZIKV-infected mouse brains. Nicotinamide riboside supplementation increases the brain and body weight as well as improves the survival in ZIKV-infected mice. Our study provides a comprehensive resource of biological data to support future investigations of ZIKV-induced microcephaly and demonstrates that metabolic alterations can be potentially exploited for developing therapeutic strategies.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Animals
Brain metabolism
Brain pathology
Brain virology
Cells, Cultured
Chromatography, Liquid
Disease Models, Animal
Disease Susceptibility
Female
Metabolomics
Mice
Microcephaly pathology
Neurons metabolism
Pregnancy
Proteomics methods
Tandem Mass Spectrometry
Microcephaly etiology
Microcephaly metabolism
NAD metabolism
Zika Virus physiology
Zika Virus Infection complications
Zika Virus Infection virology
Subjects
Details
- Language :
- English
- ISSN :
- 2522-5812
- Volume :
- 3
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nature metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 34385701
- Full Text :
- https://doi.org/10.1038/s42255-021-00437-0