Type I interferon (IFN-alpha and IFN-beta) is a secreted cytokine that binds the type I interferon receptor (IFNAR) on the surface of cells. IFNAR is a heterodimer of IFNAR1 and IFNAR2. Ligand binding brings the receptor chains together and activates the receptor-associated kinases JAK1 and TYK2. These kinases phosphorylate the transcription factors STAT1 and STAT2. Phosphorylated STAT1 and STAT2 form a heterodimer that associates with IRF9 to form the ISGF3 complex. ISGF3 moves to the nucleus and binds interferon-stimulated response elements (ISREs) in the DNA, turning on hundreds of interferon-stimulated genes (ISGs).
Among the most important ISG products are three direct antiviral effectors. Protein kinase R (PKR) is activated by dsRNA and phosphorylates the translation initiation factor eIF2-alpha, which shuts down protein synthesis and prevents viral replication. 2'-5' oligoadenylate synthetase (OAS) is also activated by dsRNA; it produces 2'-5' oligoadenylates that activate RNase L, which degrades viral and cellular RNA. Mx proteins are GTPases that interfere with viral replication, particularly of RNA viruses. In addition to these direct effectors, interferon signaling upregulates MHC class I molecules, enhancing antigen presentation to CD8+ T cells, and increases expression of NK cell activating ligands.
The system works as a feed-forward loop: interferon induces more IRF7, making the cell more sensitive to subsequent sensing, and it induces its own negative regulators such as SOCS proteins to prevent excessive damage. The overall effect is to establish an antiviral state in the cell and in surrounding tissue before the virus can spread.