The type I interferon (IFN) response is an ancient pathway in the body’s armamentarium against viruses. This defense, on a cellular level, involves inducing transcription of hundreds of IFN-stimulated genes. Using biochemical and transcriptomic approaches, IFN-stimulated genes have been thoroughly catalogued across multiple species and cell types. But their antiviral mechanisms have not been fully characterized.
Using a combination of quantitative proteomic approaches, Biochemistry and Molecular Biology researchers Eric Jan and Leonard Foster shed light on these mechanisms in a study published in Genome Biology by investigating the effects of IFN signaling on the human proteome, and mapping how IFN induces rearrangements in the protein-protein interaction network in humans.
The team identified a total of 26,000 protein interactions in IFN-stimulated and unstimulated cells. Many of these proteins are associated with human diseases and are seen exclusively within the IFN-stimulated network. The researchers also found a surprisingly broad spectrum of cellular pathways that are involved in antiviral response, with IFN-dependent protein-protein interactions mediating novel regulatory mechanisms during both transcription and translation. For instance, specific relevant interactions show modulation of a major transcription factor, STAT1, and ribosome composition changes that affect IFN-stimulated gene protein synthesis.
Mapping these interactions provides a global view of the complex cellular networks activated during the body’s response to a viral invasion, thus shedding light onto the rewiring of networks to regulate key aspects of the antiviral response. This work also places IFN-stimulated genes in a functional context, and serves as a framework for understanding how these networks are dysregulated in autoimmune or inflammatory diseases.
Read the paper
Kerr CH, Skinnider MA, Andrews DDT, Madero AM, Chan QWT, Stacey RG, Stoynov N, Jan E, Foster LJ. Dynamic rewiring of the human interactome by interferon signaling. Genome Biol. 2020 Jun 15;21(1):140. doi: 10.1186/s13059-020-02050-y. PMID: 32539747; PMCID: PMC7294662.