PXD006263

PXD006263 is an original dataset announced via ProteomeXchange.

Title	Targeting metabolic reprogramming by influenza infection for therapeutic intervention
Description	Influenza infection is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry we found metabolic changes occurring after influenza infection in primary human respiratory cells, and validated infection associate increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen and high throughput titering that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production. BEZ235 treatment ablated the transient induction of c-Myc, restored PI3K/mTOR pathway homeostasis measured by 4E-BP1 and p85 phosphorylation, and reversed infection-induced changes in glucose and glutamine metabolism. Importantly, BEZ235 reduced infectious progeny but had no effect on viral entry or the early stages of viral replication. In a lethal infection model, BEZ235 significantly increased survival while reducing viral titer and respiratory distress. Here we show metabolic reprogramming of host cells by influenza virus exposes targets for therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2017-05-24
AnnouncementXML	Submission_2017-06-07_00:21:35.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Svetlana Rezinciuc
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2017-04-05 07:43:20	ID requested
1	2017-05-24 06:21:29	announced
⏵ 2	2017-06-07 00:21:36	announced	Updated publication reference for PubMed record(s): 28538182.

Smallwood HS, Duan S, Morfouace M, Rezinciuc S, Shulkin BL, Shelat A, Zink EE, Milasta S, Bajracharya R, Oluwaseum AJ, Roussel MF, Green DR, Pasa-Tolic L, Thomas PG, Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention. Cell Rep, 19(8):1640-1653(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: PET scan, proteomics, respiratory viral infection, metabolism, influenza, BEZ235

Heather Smallwood
contact affiliation	University of Tennessee, Health Science Center, Department of Pediatrics
contact email	hsmallwo@uthsc.edu
lab head
Svetlana Rezinciuc
contact affiliation	UTHSC
contact email	srezinci@uthsc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/05/PXD006263

PRIDE project URI

• PRIDE
  1. PXD006263
     1. Label: PRIDE project
     2. Name: Targeting metabolic reprogramming by influenza infection for therapeutic intervention