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

Philipp Hubel, Christian Urban, Valter Bergant, William M. Schneider, Barbara Knauer, Alexey Stukalov, Pietro Scaturro, Angelika Mann, Linda Brunotte, Heinrich H. Hoffmann, John W. Schoggins, Martin Schwemmle, Matthias Mann, Charles M. Rice, Andreas Pichlmair

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)493-502
Number of pages10
JournalNature immunology
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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