PXD009999

PXD009999 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic-based kinase profiling early in influenza virus infection
Description	Although annual epidemics of seasonal influenza affect around 10% of the global population, current treatment options are limited and development of new antivirals is urgently needed. Here, using state-of-the-art quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. Based on this virus-induced phosphorylation signature, we uncover cellular kinases required for the observed signalling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As GRK2 has emerged as drug target in heart disease, we focus on its role in IAV infection and show that it is required for viral entry at the stage of uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in an animal model. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as a crucial node of the kinase network that enables IAV replication.
HostingRepository	PRIDE
AnnounceDate	2018-09-13
AnnouncementXML	Submission_2018-09-13_01:33:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emilio Yángüez
SpeciesList	scientific name: Influenza A virus (A/WSN/1933(H1N1)); NCBI TaxID: 382835; scientific name: Gallus gallus (Chicken); NCBI TaxID: 9031; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-01 02:04:19	ID requested
⏵ 1	2018-09-13 01:33:59	announced

Y, á, ng, ü, ez E, Hunziker A, Dobay MP, Yildiz S, Schading S, Elshina E, Karakus U, Gehrig P, Grossmann J, Dijkman R, Schmolke M, Stertz S, Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target. Nat Commun, 9(1):3679(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Influenza virus, phosphoproteomics, SILAC

Silke Stertz
contact affiliation	Institute of Medical Virology University of Zürich Winterthurerstrasse 190 CH-8057 Zürich Switzerland
contact email	stertz.silke@virology.uzh.ch
lab head
Emilio Yángüez
contact affiliation	University of Zurich
contact email	emilio.yanguez@fgcz.ethz.ch
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/2018/09/PXD009999

PRIDE project URI

• PRIDE
  1. PXD009999
     1. Label: PRIDE project
     2. Name: Phosphoproteomic-based kinase profiling early in influenza virus infection