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. 2017 Jan 31;8:49. doi: 10.3389/fimmu.2017.00049

Figure 1.

Figure 1

Induction of interferons (IFNs) and establishment of an antiviral state in a model chicken cell. The double-stranded RNA (dsRNA), detected by either chicken retinoic acid-inducible gene I (RIG-I)-like helicase (RLH) [melanoma differentiation-associated gene 5 (MDA5) or laboratory of genetics and physiology 2 (LGP2) individually or in cooperation] or toll-like receptor (TLR)3 (endosomal, phagosomal, or transmembrane) initiates downstream signaling mediated through mitochondrial antiviral-signaling protein (MAVS) or TRIF, respectively. These adaptor molecules then activate the transcription factors IFN regulatory factor (IRF)7, nuclear factor kappa B (NF-κB), and activating protein 1 (AP-1) (ATF2/JUN) by orchestrating the assembly of multi-protein complexes. Once activated, IRF7, NF-κB, and AP-1 translocate to the nucleus where they stimulate the transcription of, among others, type I IFNs (e.g., IFN-β). The transcribed, translated, and secreted type I IFNs initiate the JAK–STAT pathway by both autocrine (depicted in the figure) and paracrine signaling through cognate type I IFN receptor recognition. Activated JAK–STAT leads to the phosphorylation of STAT1 and STAT2 molecules, which (together with factors that are currently unknown in chicken) results in the formation of the IFN-stimulated gene factor 3 (ISGF3) transcription factor complex. This multifunctional transcription factor then scans and recognizes unique IFN-stimulated response element (ISRE) sequences to initiate the transcription of hundreds of chicken IFN-stimulated genes (chISGs), which subsequently establish the antiviral state against the invading viruses. Few examples of IFN-stimulated genes (ISGs) along with a summarized description of their functions are enlisted in the right panel of the figure. Abbreviations used in the figure and are not described in the main text are as follows: IκB kinase (IKK) epsilon (IKKε), alpha (IKKα), beta (IKKβ), and gamma (IKKγ); NF-κB essential modulator (NEMO); TANK-binding kinase 1 (TBK1); inhibitors of NF-κB (IκB), NF-κB subunits p50 and p65; activating transcription factor 2 (ATF2); tyrosine kinase 2 (TYK2); Janus kinase 1 (JAK1); signal transducer and activator of transcription 1 (STAT1), and STAT2. “P” represents the phosphorylation state of the protein, and dotted lines indicate the involvement of multiple intermediary steps.