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Nat Immunol. 2019 Apr;20(4):493-502. doi: 10.1038/s41590-019-0323-3. Epub 2019 Mar 4.

A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.

Author information

1
Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Munich, Germany.
2
Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany.
3
Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
4
Institute of Virology, Westfaelische Wilhelms-University Muenster, Muenster, Germany.
5
Cluster of Excellence 'Cells in Motion', Westfaelische Wilhelms-University Muenster, Muenster, Germany.
6
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
7
Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
8
Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Munich, Germany.
9
Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Munich, Germany. andreas.pichlmair@tum.de.
10
Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany. andreas.pichlmair@tum.de.
11
German Center for Infection Research (DZIF) Munich Partner Site, Munich, Germany. andreas.pichlmair@tum.de.

Abstract

Interferon-stimulated genes (ISGs) form the backbone of the innate immune system and are important for limiting intra- and intercellular viral replication and spread. We conducted a mass-spectrometry-based survey to understand the fundamental organization of the innate immune system and to explore the molecular functions of individual ISGs. We identified interactions between 104 ISGs and 1,401 cellular binding partners engaging in 2,734 high-confidence interactions. 90% of these interactions are unreported so far, and our survey therefore illuminates a far wider activity spectrum of ISGs than is currently known. Integration of the resulting ISG-interaction network with published datasets and functional studies allowed us to identify regulators of immunity and processes related to the immune system. Given the extraordinary robustness of the innate immune system, this ISG network may serve as a blueprint for therapeutic targeting of cellular systems to efficiently fight viral infections.

PMID:
30833792
DOI:
10.1038/s41590-019-0323-3
[Indexed for MEDLINE]

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