PXD026814

PXD026814 is an original dataset announced via ProteomeXchange.

Title	Aberrant NAD+ metabolism underlies Zika virus-induced microcephaly
Description	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. We perform a multi-omics study comprising transcriptomics, proteomics, phosphoproteomics, and metabolomics approaches on the brains from ZIKV-infected mice. Our proteomics and metabolomics analyses uncover dramatic alteration of nicotinamide adenine dinucleotide (NAD+)-related metabolic pathways, including oxidative phosphorylation, TCA cycle, and tryptophan metabolism. Phosphoproteomics analysis indicates that MAPK and cGMP-PKG signalling may be associated with ZIKV-induced microcephaly. Importantly, we demonstrate the utility of our rich multi-omics datasets with follow-up in vivo experiments which confirm that boosting NAD+ by NAD+ or NR supplementation alleviates cell death and increases cortex thickness in ZIKV-infected mouse brains. NR 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.
HostingRepository	iProX
AnnounceDate	2021-06-18
AnnouncementXML	Submission_2021-12-07_19:11:21.787.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yushen Wang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-20 19:41:35	ID requested
1	2021-07-25 23:16:50	announced
⏵ 2	2021-12-07 19:11:26	announced	2021-12-08: Update publication information.

Pang H, Jiang Y, Li J, Wang Y, Nie M, Xiao N, Wang S, Song Z, Ji F, Chang Y, Zheng Y, Yao K, Yao L, Li S, Li P, Song L, Lan X, Xu Z, Hu Z, metabolism underlies Zika virus-induced microcephaly. Nat Metab, 3(8):1109-1124(2021) [pubmed]

submitter keyword: ZIKA virus, Microcephaly, Transcriptomics, Proteomics,Phosphoproteomics,Metabolomics, NAD+ metabolism

Zeping Hu
contact affiliation	Tsinghua University
contact email	zeping_hu@tsinghua.edu.cn
lab head
Yushen Wang
contact affiliation	Tsinghua University
contact email	wangys17@mails.tsinghua.edu.cn
dataset submitter

iProX dataset URI