Global Interferon-stimulated Genes Interactome Network

Interferon-stimulated genes (ISGs) form the backbone of innate immune system and are pivotal 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 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 currently known. Integration of the resulting ISG-interaction network with published datasets and functional studies allowed us to identify novel regulators of immunity and immune system–related processes. Given the extraordinary robustness of the innate immune system, this ISG network may serve as a blueprint for therapeutic targeting of cellular systems in order to efficiently fight viral infections.