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

Yángüez, Emilio; Hunziker, Annika; Dobay, Maria Pamela; Yildiz, Soner; Schading, Simon; Elshina, Elizaveta; Karakus, Umut; Gehrig, Peter; Grossmann, Jonas; Dijkman, Ronald; Schmolke, Mirco; Stertz, Silke (2018). Phosphoproteomic-based kinase profiling early in influenza virus infection identifies GRK2 as antiviral drug target. Nature communications, 9(1), p. 3679. Nature Publishing Group 10.1038/s41467-018-06119-y

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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 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 uncoating. Replication of seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in primary human airway cultures and in mice. Our study reveals the IAV-induced changes to the cellular phosphoproteome and identifies GRK2 as crucial node of the kinase network that enables IAV replication.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Dijkman, Ronald

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

04 Jun 2019 15:58

Last Modified:

09 Jun 2019 02:36

Publisher DOI:

10.1038/s41467-018-06119-y

PubMed ID:

30206219

BORIS DOI:

10.7892/boris.127514

URI:

https://boris.unibe.ch/id/eprint/127514

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