Proteomics

Dataset Information

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Phosphoproteomic-based kinase profiling early in influenza virus infection


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human) Gallus Gallus (chicken) Influenza A Virus (a/wsn/1933(h1n1))

TISSUE(S): Epithelial Cell Of Lung, Cell Culture

DISEASE(S): Influenza

SUBMITTER: Emilio Yángüez  

LAB HEAD: Silke Stertz

PROVIDER: PXD009999 | Pride | 2018-09-13

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
IAVvsMock_IMAC_1.raw Raw
IAVvsMock_IMAC_2.raw Raw
IAVvsMock_IMAC_3.raw Raw
IAVvsMock_IMAC_4.raw Raw
IAVvsMock_IMAC_5.raw Raw
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Publications

Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target.

Yángüez Emilio E   Hunziker Annika A   Dobay Maria Pamela MP   Yildiz Soner S   Schading Simon S   Elshina Elizaveta E   Karakus Umut U   Gehrig Peter P   Grossmann Jonas J   Dijkman Ronald R   Schmolke Mirco M   Stertz Silke S  

Nature communications 20180911 1


Although annual influenza epidemics affect around 10% of the global population, current treatment options are limited and development of new antivirals is needed. Here, using quantitative phosphoproteomics, we reveal the unique phosphoproteome dynamics that occur in the host cell within minutes of influenza A virus (IAV) infection. We uncover cellular kinases required for the observed signaling pattern and find that inhibition of selected candidates, such as the G protein-coupled receptor kinase  ...[more]

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