Interferons (IFNs) are potent cytokines and key components in the first line of defense against viral infections1. They control the inflammation and immune response by directly inducing anti-pathogen molecular countermeasures that can inhibit virus replication2.
Three types of IFNs (type I, II, and III) are involved in fighting a viral infection. Type I and III IFNs are expressed by immune and tissue-specific cells in response to a viral infection and share important antiviral properties2,3.
An overview of the canonical and non-canonical interferon signaling pathways involved in the host antiviral response. Discover the proteins involved in these pathways and find highly validated products for your target of interest.
In the canonical pathways, interactions between type I and II IFN and their respective receptors IFNAR1/2 and IFNLR1/IL10R2 induce conformational changes, leading to activation of the receptor-associated Janus kinase (JAK) family (JAK1, JAK2, and TYK2). This activation allows for the recruitment and phosphorylation of signal transducer and activator of transcription (STAT) proteins.
The phosphorylated STATs will then dimerize and associate with IRF9 to form the IFN-stimulated gene factor 3 (ISGF3) complex. Upon translocation to the nucleus, this complex acts as transcription factors, regulating IFN-stimulated gene (ISG) expression2. Viruses, like SARS-CoV-2 or Influenza, possess structural and non-structural viral proteins that can disrupt the type I IFN canonical signaling pathway4.
In non-canonical pathways against viral infections, unphosphorylated STATs can form the unphosphorylated- ISG factor 3 (ISGF3) complex, which induces the expression of the ISG responsible for keeping cells protected from viral infections for longer2. Additionally, the CrkL:pSTAT-5 complex, formed between Crk-like protein and phosphorylated STAT5, translocates to the nucleus and regulates gene transcription via IFN-γ activated site (GAS) elements5.
1
Sadler A.J.,, Williams B.R.G. Interferon-inducible antiviral effectors Nat Rev Immunol 8 (7),559-68 (2008)
2
Stanifer M.L.,, Pervolaraki K.,, Boulant S. Differential Regulation of Type I and Type III Interferon Signaling Int J Mol Sci 20 (6),1445 (2019)
3
Hervas-Stubbs S.,, Perez-Gracia J.L.,, Rouzaut A.,, Sanmamed M.F.,, Le Bon A.L.,, Melero I. Direct Effects of Type I Interferons on Cells of the Immune System Clin Cancer Res 17 (9),2619-2627 (2011)
4
Yang E.,, Li MMH., All About the RNA: interferon-stimulated Genes that interfere with viral RNA processes Front Immunol 11 ,605024 (2020)
5
Mazewski, C., , Perez Ricardo, E.,, Fish Eleanor, N.,, Platanias Leonidas, C. Type I Interferon (IFN)-Regulated Activation of Canonical and Non-Canonical Signalling Pathways Front Immunol 11 ,3025 (2020)