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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism
  • Carrier Proteins / metabolism
  • Cell Line
  • Gene Expression
  • Glycoproteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity, Innate* / genetics
  • Interferons / physiology*
  • Mass Spectrometry
  • Protein Interaction Mapping*
  • Receptors, CCR4 / metabolism
  • Receptors, Peptide / metabolism
  • Ribonucleoproteins / metabolism
  • Viral Proteins / metabolism


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CCR4 protein, human
  • Carrier Proteins
  • Glycoproteins
  • LGALS3BP protein, human
  • Receptors, CCR4
  • Receptors, Peptide
  • Ribonucleoproteins
  • Viral Proteins
  • annexin II receptor, human
  • Interferons